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A large body of literature dealing with neurotoxicity has focused on trying to define the exact nature of cell death following a neurological insult. While there is some debate in the field, it has been shown that a number of neurons in a given population can respond to an acute insult stimulus by activating the apoptotic cascade. To what extent, however, these insults result in the classical manifestations of either apoptosis or necrosis, or whether a mixture of the two results, is highly controversial, in part dependent on the particular system utilized. In this paper, we investigate the role of particular apoptotic signals in cultured rat hippocampal neurons, following acute excitotoxicity, metabolic poisoning, and heat stress. In particular, we examine these effects by utilizing a modified herpes simplex viral vector to specifically deliver viral anti-apoptotic genes. We have selected a battery of viral genes (crmA, p35, gamma34.5, KsBcl-2) that have evolved to suppress suicidal host responses to infection. We examine these inhibitors in the face of the above classes of insults and report that each viral agent tested has a unique profile in its ability to protect hippocampal neurons following acute neurological insults. Specifically, the effects of domoic acid excitotoxicity can be alleviated only with crmA, p35 and gamma34.5 whereas all genes tested can protect against heat stress. Conversely, no genes tested can protect against metabolic poisoning by cyanide. Such a study helps us to further understand the nature of apoptotic signals in different insults.

Ribbon synapses, for example of the retina, are specialized synapses that differ from conventional, phasically active synapses in several aspects. Ribbon synapses can tonically and yet very rapidly release neurotransmitter via synaptic vesicle exocytosis. This requires an optimization of the synaptic machinery and is at least partly due to the presence of synaptic ribbons that bind large numbers of synaptic vesicles and which are believed to participate in priming synaptic vesicles for exocytosis. In this paper we analyzed whether ribbon synapses of the retina employ similar priming factors, i.e. Munc13-1, as do conventional, non-ribbon containing phasically active synapses. We found that though present in conventional synapses of the retina Munc13-1 was completely absent from ribbon-containing synapses of the retina, both in the outer as well as in the inner plexiform layer. This indicates that ribbon synapses of the retina employ other, possibly more potent priming factors than phasically active conventional synapses.

This paper describes the regeneration of severed peripheral nerve axons along collagen filaments without a tube. Two thousand collagen filaments were grafted to bridge 20 mm defects of rat sciatic nerve. The number of myelinated axons was approximately 4800 in the distal end of the nerve autograft at 8 weeks postoperatively; while in the collagen-filaments nerve guide it was 5500. The results suggested the collagen filaments guided regenerating axons effectively.

To achieve a better understanding of the parallel information processing that takes place in the nervous system, many researchers have recently begun to use multielectrode techniques to obtain high spatial- and temporal-resolution recordings of the firing patterns of neural ensembles. Apart from the complexities of acquiring and storing single unit responses from large numbers of neurons, the multielectrode technique has provided new challenges in the analysis of the responses from many simultaneously recorded neurons. This paper provides insights into the problem of coding/decoding of retinal images by ensembles of retinal ganglion cells. We have simultaneously recorded the responses of 15 ganglion cells to visual stimuli of various intensities and wavelengths and analyzed the data using discriminant analysis. Models of stimulus encoding were generated and discriminant analysis used to estimate the wavelength and intensity of the stimuli. We find that the ganglion cells we have recorded from are non-redundant encoders of these stimulus features. While single ganglion cells are poor classifiers of the stimulus parameters, examination of the responses of only a few ganglion cells greatly enhances our ability to specify the stimulus wavelength and intensity. Of the parameters studied, we find that the rate of firing of the ganglion cells provides the most information about these stimulus parameters, while the timing of the first action potential provides almost as much information. While we are not suggesting that the brain is using these variables, our results show how a population of sensory neurons can encode stimulus features and suggest that the brain could potentially deduce reliable information about stimulus features from response patterns of retinal ganglion cell populations.

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

The role of nitric oxide (NO) in inflammatory/demyelinating diseases is undergoing extensive investigation as a potential target for therapeutic intervention. However, interference with NO production has resulted in contrasting effects on the development of experimental allergic encephalomyelitis (EAE), the most widely used experimental model for multiple sclerosis (MS). Purpose of this paper was both the analysis of the individual clinical evolution of EAE induced in Lewis female rats by active immunisation and the evaluation of the effect of treatment with aminoguanidine, a selective inhibitor for the inducible isoform of nitric oxide synthase (iNOS). In our experimental model, relapse occurred in 66% of animals. Aminoguanidine treatment, started 3 days before immunisation, guaranteed a complete recovery from the acute phase and a delayed, milder relapse. Moreover, 79 days after immunisation inflammatory cellular infiltrates in the spinal cord were reduced. These data further support the involvement of NO in EAE evolution.

In the present paper, we demonstrate that the barrier properties of primary cultured epithelial cells isolated from porcine choroid plexus are regulated by cAMP-dependent signal transduction pathways in vitro. Triggering cAMP-connected cascades in cell layers grown on permeable filters with cAMP-analogues or forskolin led to a significant increase of transepithelial electrical resistances and a pronounced reduction in the permeation rate of a 4 kDa-dextran probe. In dose-response experiments using the cAMP-analogue 8-(4-chlorophenylthio)-cAMP transepithelial electrical resistances were observed to increase above a threshold concentration ranging between 10(-5.5) and 10(-5) M. Additional impedance studies performed with confluent cell layers grown on gold-film electrodes revealed that the observed changes in transepithelial resistances and presumably also in macromolecular permeation rates were not entirely caused by a reinforcement of intercellular junctions but also contained contributions from changes in the cell-substrate adhesion pattern. These inherent contributions to the electrical resistance and macromolecular permeability are caused by a restricted diffusion pathway between basal plasma membrane and culture substrate that have to be considered in data analysis, especially when leaky cell layers on filter substrates with low pore densities are used.

We previously reported the presence of Erk2 type mitogen-activated protein kinase (MAPK) and enrichment of its substrates in the post-synaptic density (PSD) fraction, and suggested a role for MAPK in the synaptic transmission and its modulation [Suzuki, T., Okumura-Noji, K., Nishida, E., ERK2-type mitogen-activated protein kinase (MAPK) and its substrates in post-synaptic density fractions from the rat brain, Neurosci. Res., 22 (1995) 277-285.]. In this paper, synaptic localization of the upstream and downstream components of a MAPK cascade was examined. We found that RSK1, Sos1, N-Shc 66 kDa, N-Shc 52 kDa, and Grb2 were present in the PSD fraction, and cPLA(2) was present in the synaptic plasma membrane fraction. RSK2, Sos2, and N-Shc 46 kDa were not present in the PSD fraction. Post-synaptic localization of RSK1 and Sos1 was confirmed by immunohistochemical examination at the electron microscopic level: the two immunoreactivities were localized in the PSDs, both in the spines and dendrites. These results suggest that all the MAPK cascade components examined were associated with PSD or the synaptic plasma membrane, suggesting the role(s) of the MAPK cascade for synaptic transmission and its regulation at post-synaptic sites.

Intense sound exposure to the chick ear produces cochlear damage and losses in auditory function. At twelve days post exposure there is considerable structural repair, although a defect on the sensory epithelium remains in the form of an incompletely healed 'patch' lesion. Auditory function significantly recovers 12 days after the exposure, but it, too, is incomplete. In this paper we describe the relationship between stimulus intensity and cochlear nerve discharge rate (the rate-intensity function) in two groups of chicks. One is exposed to damaging sound levels but allowed 12 days to recover, while the other is a group of non-exposed and age-matched control animals. Three different types of rate-intensity functions were identified; saturating, sloping, and straight. The percentage of saturating and sloping functions was compared across all characteristic frequencies in both groups of animals. A significant change was observed in the distribution of these types for recovered units with characteristic frequencies within the region of the patch lesion. In addition, the rate-intensity functions of these units exhibited a steeper slope and a higher maximum response. The distribution of rate-intensity function types and their slope and maximum responses, for units with characteristic frequencies outside of the patch lesion, was similar to those found in control ears. The changes in the cochlear nerve response in exposed chicks may be due to alterations in cochlear mechanics, hair cell or synaptic membrane properties, hair cell innervation, or the loss of a tonic suppression of afferent activity exerted by the damaged short hair cells.

In this paper, we have investigated the regulation of CCK mRNA expression in the brain after restraint stress with and without long-term treatment with the selective serotonin reuptake inhibitor sertraline. Stress alone increases CCK mRNA levels in the hippocampus, whereas no changes were found in the cerebral cortex, amygdaloid complex and thalamus. CCK mRNA expression decreases in the hippocampus, increases in the thalamus and was not modified in the cerebral cortex and amygdaloid complex after sertraline alone. CCK mRNA content was unchanged in all investigated areas after stress plus sertraline compared to control rats.

Incubation of hippocampal slices with different concentrations of creatine (0.5, 1, 10, 25 mM) results in a dose-dependent increase in intracellular phosphocreatine (PCr). Electrophysiological evidence suggests that this effect can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation. In this paper we show that incubation of brain slices with varying doses of creatine increases intracellular phosphocreatine and delays anoxic depolarization (AD) in a dose-dependent way. Specifically, addition to the incubation medium of 1 mM creatine significantly increased AD latency during hypoxia and prevented irreversible neuronal damage. Adding 0.5 mM creatine had no significant effect. Higher concentrations of creatine (up to 25 mM) did not provide any better protection. Our data also suggest a linear correlation between intracellular PCr and AD latency. These data report neural protection by exogenous creatine at concentrations lower than those usually reported in the literature.

Mature motoneurons interact with many cell types, including skeletal muscle fibres, Schwann cells, glia and various neurons. Each of these cell types is thought to provide trophic support to motoneurons, but it is not known whether the support provided by one cell type can fully substitute for the absence of a signal from another cell type. The ability of various growth factors to support motoneurons in the absence of muscle fibres, Schwann cells or long-axon synaptic input has been studied using in vivo models. However, these studies do not define the total needs of motoneurons, as local spinal influences have not been removed. In this paper, the total trophic requirement of mature motoneurons was assessed by culturing them at a low cell density, in the absence of all other cell types. Under these conditions, mature motoneurons die by apoptosis within 24 h, which is equivalent to the rate at which immature motoneurons die in vitro. This is consistent with the emerging view that mature cells are primed for apoptosis. Nine putative trophic factors (BDNF, CNTF, FGF2, GDNF, IGF I, IGF II, NT3, NT4, TGF-beta2), either alone or in combination, were unable to prevent the rapid death of the cultured motoneurons, even though some of these factors are able to attenuate the affects of less severe injuries such as axotomy or avulsion. The survival of mature motoneurons may therefore be dependent on a combination of growth factors, with at least one of the factors being distinct from the above mentioned factors.

Functional and pharmacological studies have suggested that there are muscarinic receptors (mAChRs) on the endothelial cells of major cerebral arteries, while recent immunological studies indicate that there are no mAChRs on the endothelium of brain capillaries. This difference may be because the distribution of mAChR on the endothelium varies with the type of vessel. This paper examines the distribution of mAChR on the vascular endothelium along intraparenchymal blood vessels in the rat brain by immunolabelling and laser confocal microscopy. Sections were immunostained by combinations of an anti-mAChR antibody (M35) with antibodies to endothelial (anti-GLUT1), or to smooth muscle markers (anti-actin). Antibody labellings were detected with fluorescent second antibodies. Most of the penetrating vessels bore mAChR immunolabelling which coincided over almost all the vessel surface with endothelial labelling. The mAChR immunolabelling was less widespread over the endothelium on the medium sized vessels (diameter50 microm) and only 50% of these vessels had mAChR staining on the endothelium. There was no mAChR immunostaining on the endothelium of the capillaries. In contrast with the basilar artery, there was no mAChR immunolabelling on the smooth muscle layer of the intracortical vessels. These data indicate that the intensity of mAChR immunolabelling decreases along the vascular tree from large conducting vessels to capillaries.

The involvement of GABAA and GABAB receptors in neural mechanisms responsible for the production of theta rhythms in hippocampal formation (HPC) slices is addressed in the present study. In a number of papers published in the last decade, we have demonstrated that theta-like activity can be successfully recorded in the limbic cortex maintained in vitro when the cholinergic agonists, acetylcholine, carbachol or muscarine, were added to the bath. Recently, we have also shown a strong GABAA modulation of the cholinergic-induced in vitro theta-like activity. This study presents a report of the first demonstration of in vitro theta-like field responses induced a consequence of simultaneously inhibiting hippocampal GABAA and GABAB receptors. HPC slices (350 microns) were maintained in a gas-liquid interface chamber (35 degrees C). Theta-like activity was induced in the presence of bath perfusion of bicuculline (GABAA antagonist) and 2-hydroxysaclophen (GABAB antagonist). This in vitro induced field response was antagonized both by muscimol (GABAA agonist) and baclophen (GABAB agonist). In addition, the experiments presented here revealed that bicuculline/2-hydroxysaclophen-induced in vitro theta-like activity also had a strong cholinergic M1 involvement: it was abolished by hemicholinium-3 (choline transport blocker) and pirenzepine (specific antagonist of M1 receptor), but not by gallamine (specific antagonist of M2 receptor). The results of the present study provided further evidence for a strong GABAergic/cholinergic interaction in the neural mechanism responsible for production of theta-like activity in the hippocampal formation slices.

The hallmark of Alzheimer's disease is the cerebral deposition of amyloid which is derived from the amyloid precursor protein (APP). The function of APP is unknown but there is increasing evidence for the role of APP in cell-cell and/or cell-matrix interactions. Primary cultures of murine neurons were treated with antisense oligonucleotides to down-regulate APP. This paper presents evidence that APP mediates a substrate-specific interaction between neurons and extracellular matrix components collagen type I, laminin and heparan sulphate proteoglycan but not fibronectin or poly-L-lysine. It remains to be determined whether this effect is the direct result of APP-matrix interactions, or whether an intermediary pathway is involved. (C) 1997 Elsevier Science B.V.

Alongside GABA, glycine is the major inhibitory transmitter in the central nervous system. Application of the glycine receptor blocker strychnine is known to evoke epileptiform phenomena. The present paper addresses the question whether postsynaptic calcium currents through L-type channels contribute to strychnine-induced epileptiform field potentials (EFP). To test for this, the antiepileptic effect of the specific L-type calcium channel blocker, verapamil, in hippocampal and neocortical slices was investigated. In parallel with this, the antiepileptic efficacy of the unspecific calcium channel modulator, flunarizine, was tested with respect to pharmacotherapy of epilepsies. In both preparations, the L-type calcium channel blocker, verapamil, was able to suppress EFP. In neocortical slices, EFP were blocked in all experiments, whereas in hippocampal slices, in 3 out of 11 experiments, no complete suppression occurred. Flunarizine acted in a similar way. It is concluded that L-type calcium channels are involved in strychnine-induced epilepsy, but to a greater extent in the neocortex than in the hippocampus.

This paper evaluates the changes of cytochrome oxidase (CO) activity that take place in the suprachiasmatic nucleus (SCN) during the light-dark cycle. CO is a mitochondrial energy-generating enzyme used as a marker of neural oxidative metabolism. We measured CO activity using quantitative histochemistry calibrated with brain tissue standards and a computerized analysis image system. The results indicate that the CO enzyme activity changes on the basis of a circadian pattern, with the higher levels during the light phase (P0.0001). These changes are detected over a period of hours, in accordance with other studies on the possible short-term regulation of CO activity in the nervous system. It is, therefore, possible to apply this methodology to the study of the SCN and other brain areas which show functional rhythmicity.

Previous work from this laboratory indicated that some antipsychotic drugs possess unique action at N-methyl-D-aspartate (NMDA) receptors. A functional neurochemical assay showed that, at concentrations similar to those found in the cerebrospinal fluid (CSF) of schizophrenics, antipsychotic drugs augment NMDA activity while, at higher concentrations, NMDA activity is suppressed. Using similar analysis, the present paper reports that this pattern of response is also shown by the antipsychotic drugs thioridazine and chlorpromazine. In contrast, promazine, which is structurally similar to chlorpromazine but lacking both D2-effects and antipsychotic potency, had no influence on NMDA receptors. In addition, sulpiride and metoclopramide, drugs with high affinity for D2-dopamine receptors but with weak or no antipsychotic efficacy, also lack effects at the NMDA receptor. Thus, the drugs with clinical efficacy that were tested in the present and previous studies all share unique influence on NMDA receptors. Further work with other antipsychotic agents will be necessary to determine if influence on NMDA receptors contributes to antipsychotic effectiveness.

In order to study interocular temporal coupling in the initiation of learned symmetrical blinking, experiments were carried out on cats trained to blink in response to a 500-ms tone paired with 100-ms airpuffs randomly delivered to either eye (alternate airpuff; 6 animals) or simultaneously directed to both eyes (bilateral airpuff; 4 animals) 400 ms after tone onset. In spite of the fact that differences in conditioned response (CR) latencies of the right and left eye varied in a wide range between positive and negative values in all subjects, a statistically significant difference between the mean CR latencies of the two eyes (further called side superiority) was found in 6 animals, of which 4 were trained by alternate airpuff and 2 by bilateral airpuff. Superiority of the right eye was found in 3 animals and the opposite was observed in the other 3. Analysis of the differences between CR latencies of the two eyes showed that side superiority was not due to the ability of one eye to give CRs consistently shorter than those of the other eye, but it crucially depended on the higher proportion of trials in which the superior eye led. The ability to give simultaneous CRs by the two eyes was found inversely related to the mean CR latency per session and subject. Regression analysis showed that power equations best described these relationships. In all animals, the frequency distribution of simultaneous CRs paralleled the frequency distribution of all CRs. In spite of a considerable trial-by-trial variability in the temporal relationships between CR latencies of the two eyes, clear-cut linear correlations were found by plotting the mean CR latencies of the right and left eye per both session and subject. The results reviewed in this paper are best accounted for by suggesting that blink onset of the two eyes is independently controlled by two distinct command signals and is modulated by bilaterally-balanced and lateralized influences.

The mechanism and regulation of iron transport to the brain are largely unknown. The large surface area of the blood–brain barrier capillaries and the presence of transferrin receptors on the luminal plasma membranes of the blood–brain barrier endothelial cells (BBB-ECs) suggest that these cells actively participate in the transport of iron into the brain. In this paper, we describe the ultrastructural morphology of primary and first-passage cultures of BBB-ECs grown on different types of porous membranes. To investigate the mechanism of iron transport into and across the BBB-ECs, porous membrane grown first-passage cells were incubated with 6.6-nm gold-labeled transferrin and studied with electron microscopy. Results are suggestive for a transcytosis of transferrin through the BBB-ECs.

Using an antibody against microtubule associated protein 2 (MAP-2; a specific marker for neuronal dendrites), this paper reports the structural organisation of pyramidal cell apical dendrites in the rat prelimbic (PL) cortex. In the coronal plane, MAP-2-immunoreactive apical dendrites of pyramidal neurons in layers 5, 3 and 2 were found bundled together as they ascended radially through the cortex. These bundles of dendrites dispersed in upper layer 2 to form apical dendritic tufts in layer 1. In tangential cross-section, the immunolabelled bundles were organised into a latticework of discrete clusters of differentially sized profiles. At the boundary between layers 3 and 5, clusters were composed of 26 +/- 8 dendritic profiles (group mean value +/- S.D., five animals), whereas clusters in layer 2 contained 55 +/- 15 profiles. The number of clusters per unit surface area was not significantly different throughout layers 5, 3 and 2 (760 +/- 75 per mm2) with the average centre-to-centre intercluster distance in these layers being 44.2 +/- 4.9 microns. The data indicate that apical dendritic bundles are a feature of the radial organisation of PL cortex. These structural subunits may subserve specific integrative functions in the PL area of the rat medial prefrontal cortex.

Recent publications have reported calcium level determinations in slices of brain using imaging techniques and the dye fura-2AM. In general these studies ignore or deal only perfunctorily with the problem of autofluorescence in slices. This confound, which is a result of the pyridine nucleotides that are normally present in tissue, has been previously reported to interfere with Ca2+ measurements in slices. Because these pyridine compounds are involved in cell metabolism, the fluorescence intensity is labile over time following experimental manipulations. We were studying Ca2+ levels in hippocampal slices using standard imaging techniques. We found significant and variable autofluorescence at the wavelengths used for calcium determination which interfered with data interpretation in fura-treated slices. The intensity of this autofluorescence is an additive effect and is not large enough to be observed when imaging monolayers. In this paper we present a method for conducting experiments and analyzing data that decreases interference from autofluorescence. Experiments were carried out on both slices bulk loaded with fura-2AM and slices loaded with control buffer. A point to point subtraction of the control slice values gave representative calcium fluorescence values. Hippocampal slices were challenged with sodium cyanide or kainic acid. The metabolic response, seen in the fura-free slices, and the calcium response varied within and between these two treatments. Regional differences in the hippocampal sub fields were also demonstrated in response to the two treatments. These corresponded to known regional vulnerabilities to cyanide and kainate. We conclude that autofluorescence in slices need be considered when determining calcium concentrations using fura-2AM.

Neurons require a mechanism to transmit stable signals over the large distance from the nerve growth cone or terminal to the cell body, in order that information from the target tissue can be relayed to the cell body where it is required. Nerve growth factor (NGF), a target-derived neurotrophic factor, is thought to signal over this distance by receptor mediated internalization of NGF, followed by retrograde axonal transport of the NGF-receptor complex. In this paper we show, by immunohistochemistry of rat sciatic nerve, accumulation of phosphotyrosine immunoreactivity only on the distal side of a nerve crush, suggesting axonal transport of tyrosine kinases and/or tyrosine phosphorylated proteins primarily in a retrograde direction. Furthermore, we also show retrograde axonal transport of phosphoinositide 3-kinase, ERK, MEK and MEK kinase, of which all but MEK kinase are known to be activated downstream of tyrosine receptor kinase activation. The retrograde transport of these proteins suggests that they may be involved in transmission of signals along the axon, relaying neurotrophic factor receptor activation at the nerve terminal to the nerve cell body.

The present paper sought to test the hypothesis that inhibitory glycine receptors (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are involved in the inhibition of the acoustic startle response (ASR) in rats. First we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR on PnC neurons by immunocytochemical labeling using an antibody against the alpha 1 subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting phenomena, short-term habituation and prepulse inhibition, after microinjections of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist beta-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor beta-alanine had a measurable influence on any of the parameters of the ASR investigated (amplitude, short-term habituation, prepulse inhibition). In contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR amplitude. The systemic administration of strychnine did not impair prepulse inhibition. The human 'startle disease' (hyperekplexia), an exaggerated startle response, is caused by a defect of the alpha 1 subunit of the inhibitory GlyR, but it is unclear at which site in the central nervous system this defect ultimately leads to the symptoms of hyperekplexia. Our data indicate that a blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats, suggesting that deficient GlyRs in the PnC might not be involved in the etiology of the human 'startle disease'. We conclude that the inhibitory GlyRs on PnC neurons are not necessary for the inhibition of the ASR and believe that they are involved in another behavioral context.

In this paper we report on the effects of intra-VTA infusion of opioid agonists on rat ingestive behavior in a variety of experimental contexts. When the animals were tested outside of their home cages surrounded only by food-pellets (Experiment 1), the injection of the mu-opioid agonist DAMGO, but not the kappa-opioid agonist U-50,488H, into the ventral tegmental area facilitated food-related behaviors, decreasing the latency to feed and increasing the number of interactions with food. When, as in Experiment 2, gnawable objects and a drinking tube were also available, intra-VTA DAMGO gnawing and drinking behaviors, whereas the effects on feeding were negligible. These effects intra-VTA DAMGO increased were greatly enhanced in rats that underwent repeated treatments with amphetamine. On the other hand, when food-related behaviors were studied in a home-cage, where access to the food supply was achieved by entry into a tunnel, latency to feed and total food-intake were not enhanced in tests made during either the dark or the light phase (Experiment 3 and 4). This was true whether powdered standard lab chow or a highly palatable food was available. It appears that when a number of alternative incentive stimuli are available, increases in dopamine transmission such as that induced by intra-VTA DAMGO may ultimately have the effect of interfering with behavior normally directed primarily to one of these stimuli, by enhancing the salience of others. These effects bears some resemblance to the effects of tail-pinch and electrical brain stimulation of the medial forebrain bundle-lateral hypothalamic area on the responses to natural incentive stimuli.

In calcium-free media, neurones in the rat hippocampal slice develop bursts of population potentials and lose their sensitivity to adenosine. The present paper reports the unexpected and paradoxical finding that the xanthines theophylline and cyclopentyltheophylline, the latter of which is selective for A 1 purine receptors, depressed the excitability of hippocampal pyramidal neurones in calcium-free media. Chelating residual calcium with EGTA reduced excitability which was additive with the xanthine effect, while 100 μM calcium depressed the response to theophylline. The inhibition by xanthines was prevented by adenosine, which had no effect by itself, but was not reproduced or modified by adenosine deaminase. The xanthine effects were also prevented by baclofen and carbamazepine. A common feature of adenosine, baclofen and carbamazepine which may account for their antagonism of the xanthines is the blockade of calcium fluxes. It is proposed that in the presence of low external concentrations of calcium xanthines can reduce excitability by promoting the mobilisation and trans-membrane movement of residual calcium in the medium or neuronal membranes.

Secretory phospholipase A2 type II is known to be involved in various inflammatory processes. This paper describes the changes in secretory phospholipase A2 (PLA2) gene expression induced by ischemia and endotoxic shock. Type I PLA2 (pancreatic type) is not expressed in ischemic and endotoxic-shock brains but both ischemia and endotoxin injection induce type II PLA2 expression. The first phase of PLA2 II gene expression following the ischemic insult occurs 1-6 h after ischemia. During that period, PLA2 II gene expression is slightly enhanced and it returns to control levels after 1 day. A second phase corresponding to higher levels of induction of mRNA for PLA2 appears at a later period after ischemia between 7 and 18 days. In situ hybridization shows that PLA2 gene expression in the ischemic brain is localized in regions known to be vulnerable to ischemia (hippocampus and neocortex). Endotoxic shock which leads to a major inflammatory state induces an abundant expression of the PLA2 II mRNA in the brain and this high level of expression appears in a large number of brain structures. The results suggest that the early phase of ischemia-induced PLA2 gene expression could be an additional element in mechanisms leading to neuronal death. The later phase of increased PLA2 mRNA levels is more probably related to the inflammatory response associated to neuronal degeneration.

Embryonic rat olfactory bulbs were transplanted into the site vacated by aspiration of an olfactory bulb from a neonatal rat. This paper presents our findings related to the development of glial fibrillary acidic protein (GFAP) positive (+ve) glial cells and the appearance of laminin-like immunoreactivity in these transplants. The GFAP+ve glial cells formed perivascular end-feet on the invading vasculature and formed a glia limitans along the pial surface of the transplant. This reconstituted glia limitans was continuous with that of the host brain, there being no glia limitans at the donor-host interface. Thus, the donor tissue was well-integrated with that of the host brain.

Acetylcholine (ACh) is considered as the most likely candidate for a neurotransmitter of the efferent synapse onto hair cell. In this paper, the nature of this cholinergic receptor mechanism on dissociated bullfrog saccular hair cell was examined by using whole cell recording and Ca 2+ sensitive fluorophotometric technique. Bothe ACh-induced current and the increase of [Ca 2+ ] i were observed in an oscillatory manner, and were the largest around the basal part of the cell where the efferent synapse is thought to make a contact with the membrane. The reversal potential of ACh-induced current indicated that ACh activated a K + conductance. The ACh-induced current was reversibly blocked by atropine, d-tubocurarine (dTC), apamin, tetraethylammonium (TEA) and quinine. Neither muscarine nor nicotine mimicked the ACh-induced current. When GTPγS was injected into a hair cell, the first ACh application induced an outward current of transient kinetics, but in subsequent trials ACh-induced current lost its decay phase. Intracellularly injected d -myo-inositol 1,4,5-trisphosphate (InsP 3 ) generated outward currents. Intracellularly injected heparin suppressed ACh-induced currents, and lithium (Li + ) increased ACh-induced currents. These results indicate that ACh activates a receptor coupled with a guanine nucleotide binding protein (G-protein) which triggers metabolic cascades of InsP 3 and Ca 2+ leading to the activation of the Ca 2+ -activated K + channel.

To our knowledge, no brain derived cell line has been shown as yet to bear cholecystokinin(CCK)B receptors. In this paper, CCK binding sites were identified on rat C6 glioma cells. Pharmacological characterization demonstrated a single class of high affinity binding sites (Kd = 1.7 +/- 0.3 x 10(-10) M) and a binding capacity of 6.1 +/- 1.8 fmol/mg protein. These CCK binding sites displayed a typical CCKB pharmacological profile as shown in competition studies by using several CCK-related compounds and nonpeptide CCK antagonists discriminating between CCKA and CCKB sites. In order to demonstrate that CCK binding sites constitute a functional receptor CCK-8S induced mobilization of free intracellular calcium was investigated in single C6 cells by using a laser scanning confocal imaging system. Since rise in [Ca2+]i noted by stimulation of C6 cells with CCK-8S could be blocked by the CCKB receptor antagonist L-365,260 (100 nM) but not by the CCKA receptor antagonist L-364,718 (100 nM), CCK induced calcium signal is triggered by activation of CCKB receptors in C6 cells. The rat C6 glioma cell line may serve as a useful model for studying CCKB receptor in brain.

The Utah Intracortical Electrode Array is a unique silicon-based monolithic structure designed for use as a multichannel interface to the central nervous system. In this paper, we describe a series of acute experiments designed to determine the neural recording capabilities of this electrode array and the dependence of the signal-to-noise ratio (SNR) of the recordings on the electrode surface area (length of metallized tip). We found that both separable unit and multiunit cluster responses could be recorded. Additionally, high SNR recordings could be achieved for some electrodes (with electrode tip lengths of 30–220 μm), while recordings with signals substantially greater than the noise could be made from most of the electrode provided that the proper electrode surface area was used. The demonstrated recording capabilities of the Utah Intracortical Electrode Array and its unique three-dimensional structure should form the basis for innovative physiological investigations into the functional organization of the cortex as well as for long term neuroprosthesis development.

Procholinergic drugs have failed to overcome the memory deficit induced by alterations of the cholinergic system because their neurochemical target in the brain is either lacking or disorganised. However, there are many reports on a relative involvement of the dopaminergic system in learning and memory that may compensate for the cholinergic deficit because of the interaction or balance between neurotransmitters and the redundancy of the brain. The aim of our experiments is to examine the activation of the dopaminergic system on the performance of normal and medial septal lesioned rats in the radial maze test involving continuous choices. In the first experiment different groups of normal rats were treated with either 0.5, 1.0 or 2.0 mg/kg of D-amphetamine and tested in the radial maze. In the second experiment, medial septal lesioned rats which had learnt pre-op the radial maze test were retested a month later. Amphetamine had no effect on the memory measures provided by the radial maze test in normal and lesioned rats, but non-memory measures were significantly affected: amphetamine decreased the sequential choice responses and the time taken by the rats to perform the test. The present results show that the activation of the dopaminergic system does not compensate for the alteration of the cholinergic activity inducing amnesia, however, they support the recent data on the improving effect of amphetamine on locomotor activity. The interpretation of drug/lesion interaction effects is discussed in this paper in relation to the literature on the effect of promnesic drugs.

Characteristics of neural corticosteroid receptors were studied in 51 adrenally-intact macaque monkeys using a modification of a corticosteroid receptor assay developed in this laboratory for rodent studies. Using cortisol as a ligand, two receptor subtypes could be distinguished and with similar Kd's to those observed in rodents, as measured with corticosterone. The time course showed maximum binding for mineralocorticoid receptors at 24 h and for glucocorticoid at 4 h. There were regional differences in the number of available binding sites for each receptor type, as well as an inverse correlation between the concentration of cortisol in the blood at the time of death and the number of available binding sites. In general this paper emphasizes the similarities between such receptors in primate and those in other species, similarities that could be detected despite the technical constraints of studying tissue taken from non-adrenalectomized animals.

A population of neurons immunoreactive to an antiserum (AS) raised against ovine prolactin (LHPLI neurons) was previously described in the rat perifornical areas and lateral hypothalamus. In the present paper, we demonstrate by complementary immunocytochemical studies using AS to various biologically active peptides or neurotransmitters that these neurons are also detected by AS to bradykinin and to dynorphin B. Electron microscope examination shows that the LHPLI neurons are peptidergic neurons synthesizing apparently only one type of secretory granules. Numerous synapses on their perikarya and processes reflect the complexity of their relationships with other neuron populations, which have yet to be mapped and elucidated.

The visual system is hierarchically organized between and within areas. Previous studies have found that aging affects different visual areas in a progressive manner, e.g. more degradation occurs in the primary visual cortex (V1) than in the dorsal lateral geniculate nucleus (dLGN), and more in the secondary visual (V2) and middle temporal (MT) visual areas than in V1. In view of these findings, we hypothesize that higher levels within the visual information hierarchy are affected more severely by aging. Hierarchies exist not only between visual areas but also within areas (e.g. V1, has a simple to complex cell hierarchy). We expected that a similar pattern of ageing effects should be found within a given visual area. To study this question, primary visual cortex is a good candidate because there is good evidence for the simple to complex cell hierarchy. In this paper, we applied single unit recording techniques to study the visual response properties of V1 simple and complex cells in young and old monkeys in vivo. We found that the orientation and direction selectivity of complex cells were significantly degraded in old monkeys, while those of simple cells were relatively spared from the effects of aging. These findings are consistent with the hypothesis that higher hierarchical levels in the visual system, both between and within areas, may be affected more severely by aging.

The aim of this paper was to examine if pre- and neonatal exposure that results in lead (Pb) concentration below ‘safe level’ (10 μg/dL) in offspring blood may cause disruption of the pro/antioxidant balance in the developing rat brain. We studied oxidative stress intensity (malondialdehyde (MDA) concentration) as well as mRNA, protein expression and the activity of copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (GPx4), catalase (CAT), glutathione reductase (GSR). We also measured glutathione (GSH) concentrations in selected structures of the rat brain (forebrain cortex, FC, cerebellum, C, and hippocampus, H) and showed cellular localization of GPx4, SOD1 and SOD2 expressions in the hippocampus by immunohistochemical examinations. Despite low Pb level in blood we observed decrease of the activity of some antioxidant enzymes as well as mRNA and protein expression downregulation associated with an increase of MDA level and CAT expression upregulation, especially in the hippocampus region. At the subcellular level, downregulation of SOD2 expression and decreased enzyme activity as well as mitochondrial pool of GSH suggest also that mitochondrial mechanisms might account for Pb neurotoxicity mechanism. For some enzymes, we found differences in the effects of Pb on the level of expression and activity. The activity of CAT decreased despite an increase in mRNA and protein expression; and likewise the activities SOD1, GPx1 GPx4 decreased, despite substantially unchanged level of expression. These effects may be the result of impairment of catalytic function of the enzyme protein caused by Pb interaction or of reduction in the availability of cofactors. We conclude that antioxidant system of the hippocampus of immature rat brain is highly vulnerable to perinatal Pb exposure. Therefore, oxidative stress may be one of the possible mechanisms disturbing cellular metabolism in this structure. Disruption of pro- and antioxidant balance should be considered as a potential mechanism of the observed Pb adverse effects, leading to the impaired learning ability caused by Pb exposure in children.

Exposure of frog skeletal muscle to a Ringer solution made hyperosmotic with glycerol, followed by return of the preparation to a normal Ringer, results in an irreversible uncoupling of the mechanical activity of the muscle. This technique for preventing muscle contraction has often been used to study neuromuscular transmission under normal or high levels of release without interference from muscle contraction. Little was known, however, about the effects of glycerol treatment on the process of transmitter release. In this paper we report the results of a study in which we examined the effects of glycerol treatment on transmitter release during repetitive stimulation at the frog sartorius neuromuscular junction. We found that glycerol treatment altered the stimulation-induced changes in end-plate potential (EPP) amplitude normally observed during repetitive stimulation at this synapse. This effect, which increased progressively with time for up to 8 h following removal of glycerol, could be accounted for by presynaptic changes in the amount of transmitter released.

In the present paper, the distribution of a neuron-specific phosphoneuroprotein 14 (PNP 14) in cell and tissue was investigated in detail by the immunoblot method using affinity-purified antibody against this protein. The immunoblot of the supernatant fractions of various tissue homogenates of rat clearly demonstrated that PNP 14 was enormously rich in the brain. The content in rat brain was as much as 0.1% of the homogenate. The immunocytochemical study showed that the protein was localized at nerve endings in the cerebellum. Existence of the protein was also confirmed in cultured neuronal cells from postnatal rat midbrain, but not in glial cells. Examination of subcellular localization of PNP 14 indicates that the protein was present in synaptic plasma membranes and synaptic supernatant fractions, but not in synaptic vesicles. During the development of rat brain, PNP 14 came into existence after birth and it's amount linearly increased to a maximum at 21-28 days after birth. The content of the protein then remained at the same level for more than 10 months. We concluded that this protein is neuron specific and supposed that it may be involved in neuronal formation and function.

In the present paper, the effect of different stressors on extracellular 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the frontal cortex and the N. raphe dorsalis (NRD) of the rat were studied. The following stressful procedures were used: Immobilization, 10 min, cold, 20 min, and forced exercise in a rotating wheel, 2h. These procedures were compared with a handling procedure, 10 min. The extracellular 5-HIAA concentration was followed by in vivo voltammetry with carbon multifibre electrodes in the awake animal. Handling had no significant effect on extracellular 5-HIAA concentrations neither in the frontal cortex nor the NRD, whereas immobilization and cold evoked significant increases in both brain areas. During and after forced exercise a significant increase was measurable only in the frontal cortex, while extracellular 5-HIAA concentrations were unchanged in the NRD. Since it is very likely that the modulation of the activity of the central serotoninergic system under stressful conditions is closely connected with changes in behaviour and temperature regulation, we compared our findings on extracellular 5-HIAA levels during stress with the effect of the 5-HT1A agonist (+)-8-hydroxy-2-(di-n-propyyamino)tetraline (8-OH-DPAT), a substance known to reduce body temperature. The i.p. injection of a low dose decreased significantly both, the extracellular 5-HIAA concentration in the NRD and body temperature. Our result suggest that the serotoninergic activation in the frontal cortex may prove to be a general response to stress which could function perhaps as a part of the central coping mechanism, whereas serotonin (5-HT) in the NRD may modulate specific regulatory responses such as body temperature.

The initiation site of seizure discharges and the relationship between behavioral manifestations and electroencephalography were investigated in the El mouse, a hereditary epilepsy model. The chronic depth electrodes were implanted stereotaxically into the frontal cortex, parietal cortex, temporal cortex, hippocampus, striatum, amygdaloid complex, non-specific nuclei of thalamus and substantia nigra. Electrical activities were recorded in freely moving condition with use of the buffer amplifier devised in the laboratory and behaviors were monitored simultaneously. Seizure spike discharges started in the parietal cortex and spread out into other brain areas. When the hippocampus was involved, the tonic convulsion occurred behaviorally. The paper describes the first direct evidence of the initiation and propagation of seizure discharges in the brain of El mouse.

This study addressed the issue of multiple parallel auditory processing systems and their relationship to the skull-recorded auditory evoked potentials (AEPs) in the unanesthetized, unrestrained rat. In the preceding paper (Brain Res., 602 (1993) 240–250) it has been shown that auditory cortex activity does not contribute significantly to the vertex maximal AEPs recorded from the dorsal skull of the rat. In the present study, mapping of the AEP skull distribution revealed two sets of components: one set maximal at the dorsal skull vertex, and another set maximal at the lateral skull over auditory cortex. Barbiturate anesthesia eliminated the dorsal skull maximal components (and later components at the lateral skull), but not the early (P7–P11, N15) lateral skull components generated in auditory cortex. Bilateral auditory cortex ablation eliminated the lateral skull maximal AEP components, but not the dorsal skull maximal components. These findings support extensive parallel processing of auditory inputs (reflected by the dorsal AEPs) in the absence of primary auditorycortex. Ablation of primary auditory cortex did result in a modulation of the dorsal skull AEPs, indicative of an interaction between the geniculocortical system and the parallel system which generates the dorsal AEPs.

At present severe damage to hair cells and sensory neurons in the inner ear results in non-treatable auditory disorders. Cell implantation is a potential treatment for various neurological disorders and has already been used in clinical practice. In the inner ear, delivery of therapeutic substances including neurotrophic factors and stem cells provide strategies that in the future may ameliorate or restore hearing impairment. In order to describe a surgical auditory nerve trunk approach, in the present paper we injected the neuronal tracer horseradish peroxidase (HRP) into the central part of the nerve by an intra cranial approach. We further evaluated the applicability of the present approach by implanting statoacoustic ganglion (SAG) cells into the same location of the auditory nerve in normal hearing rats or animals deafened by application of β-bungarotoxin to the round window niche. The HRP results illustrate labeling in the cochlear nucleus in the brain stem as well as peripherally in the spiral ganglion neurons in the cochlea. The transplanted SAGs were observed within the auditory nerve trunk but no more peripheral than the CNS-PNS transitional zone. Interestingly, the auditory nerve injection did not impair auditory function, as evidenced by the auditory brainstem response. The present findings illustrate that an auditory nerve trunk approach may well access the entire auditory nerve and does not compromise auditory function. We suggest that such an approach might compose a suitable route for cell transplantation into this sensory cranial nerve.

Our previous study showed that when stimulated with constant frequency–frequency modulation (CF–FM) sounds, neurons in the central nucleus of the inferior colliculus of the CF–FM bat, Hipposideros armiger, either only discharged impulses to the onset of CF–FM sounds (76%, single-on neurons) or to the onset of both CF and FM components of CF–FM sounds (24%, double-on neuron) (Fu et al., 2010). The present paper reports the recovery cycles of these two types of neurons using paired CF, FM and CF–FM sounds as stimuli. Both types of neurons had similar recovery cycle for CF sounds but had the shortest recovery cycle for FM sounds. Whereas single-on neurons had similar recovery cycle for CF and CF–FM sounds, double-on neurons had longer recovery cycle for CF sounds than for CF–FM sounds. In addition, double-on neurons had significantly shorter recovery cycles than single-on neurons for FM and CF–FM sounds. Most neurons did not respond to the second sound when each pair of sounds overlapped. However, when stimulated with paired CF–FM sounds, 3 single-on and 7 double-on neurons discharged to the second sound even when both sounds overlapped. As such, they had “cyclic” recovery cycles that varied between maximum and minimum with inter-pulse intervals. Possible mechanisms underlying the different recovery cycles of these neurons are proposed. Possible biological significance of these neurons in relation to responding to varied pulse repetition rate during hunting is discussed.

The anticonvulsant effect of 1-naphthylacetyl spermine, an analogue of Joro spider toxin (JSTX), was studied against seizures induced by quisqualate (QUIS), a non-NMDA agonist, as assessed electrophysiologically and behaviorally in freely moving rats. Electrodes were implanted into right dorsal hippocampus and an injection cannula ofr drugs into right ventricle. The pretreatment with JSTX analogue significantly inhibited both of QUIS-induced hippocampal discharges (80-11%) and generalized tonic clonic seizures (100-33%) in a dose-dependent manner, whereas JSTX had no effect no seizures induced by quinolinate, a NMDA agonist. The paper provides the first direct evidence that the JSTX analogue exerts a potent and selective suppression of hippocampal epileptic discharges mediated by non- N -methyl- d -asparta (non-NMDA) receptors.

Demyelination of central axons arises from a number of conditions, including multiple sclerosis and spinal cord compression. The demyelination disrupts conduction and leads directly to the production of symptoms. Repair of the demyelination by peripheral myelinating cells could potentially relieve the symptoms, but the conduction properties of central axons remyelinated by Schwann cells have yet to be studied in detail. This paper examined the conduction properties of such axons. Large focal demyelinating and remyelinating lesions were induced in the dorsal columns of rats by the intraspinal injection of ethidium bromide. Recordings of compound action potentials conducted through these lesions were then made at various recovery times. Thus the changing conduction properties of the affected fibers could be correlated with the different stages of lesion development. During the early stages of demyelination there was widespread conduction block, with no evidence of appreciable conduction occurring with prolonged latency or refractory period of transmission (RPT). However, with the onset of remyelination by Schwann cells, conduction was restored in many axons, and most, if not all, of the affected axons eventually showed successful conduction through the lesion. Initially the conduction was characterized by very prolonged latency, long RPT, and an inability to conduct fast trains of impulses. These deficits became less prominent as remyelination progressed. In chronically remyelinated axons the RPT was restored to within normal limits, although some deficit in both conduction velocity and the ability to conduct trains of impulses persisted. Since these deficits were not severe we conclude that remyelination of central demyelinated axons by Schwann cells should be effective in promoting the restoration of normal function.

In this paper report the effects of peripheral (intraperitoneal, i.p.) and central (intracerebroventricular, i.c.v.) injection of selective cholecystokinin (CCK) receptor agonists on food intake in the rat. Stimulation of peripheral and central CCK-A receptors by the selective CCK-A receptor agonist A-71623 suppressed intakes of a liquid diet in both deprived and sated rats. In contrast, i.c.v., but not i.p., injections of the selective CCK-B receptor agonist A-63387, reduced food intakes, although on a molar basis the effect was much less than that seen with A-71623. Although these results stress the relative importance of the CCK-A receptor in the effects of exogenous CCK-8 administration on feeding, stimulation of the CCK-B receptor may still be involved in the control of feeding following the endogenous release of CCK.

Microinjection of a wide range of sedative agents, including triazolam, pentobarbital, ethanol and adenosine, into the medial preoptic area has been shown to increase sleep, suggesting that it is an important (though not necessarily the only) anatomic site mediating hypnotic effects of these compounds. The mechanism by which adenosine increases sleep at this site is not clear, but one possibility is that this is related to its effects on the GABA(A)-benzodiazepine receptor complex. In order to assess this possibility, this paper describes the administration of adenosine, alone and in combination with the benzodiazepine receptor blocker flumazenil, into the MPA. It was found that 12.5 and 25 nM of adenosine significantly reduced sleep latency and increased total sleep time. The sleep-inducing effect was blocked by flumazenil. Flumazenil caused a modest increase in total sleep, and prevented the increase in total sleep induced by the higher dose of adenosine. These data suggest that at least one aspect of the hypnotic properties of adenosine is mediated by a direct or indirect action on the GABA(A)-benzodiazepine receptor complex.

Background : Based on circumstantial evidences, we (Gallyas, F., Farkas, O., Mazlo, M., 2004. Gel-to-gel phase transition may occur in mammalian cells: Mechanism of formation of “dark” (compacted) neurons. Biol. Cell 96, 313–324.) proposed that the formation of “dark” neurons (striking compaction of visibly normal ultrastructural elements accompanied with large-scale fluid excretion), which occur in many neurological diseases such as ischemia, proceeds with a non-enzymatic mechanism. Objective: To support this proposition, the present paper deals with the results of supravital experiments using microwave irradiation. Method: After transcardial glutaraldehyde fixation followed by decapitation, a pin was stuck into rat brains just before and just after they were warmed up to 80 °C and maintained at this temperature for various periods of time by controlled microwave irradiation. Results: Independently of the duration of irradiation, the pre-irradiation pin sticking produced numerous “dark” neurons in an approximating 500-μm-wide zone around its track whereas the post-irradiation pin sticking did the same only when the irradiation was shorter than 55 s. The excreted fluid was present in neighbouring astrocytic processes but not in the extracellular space. Conclusions: The formation of “dark” neurons is completed in less than 55 s under the circumstances of the experiment. As neurons are poor in readily consumable chemical energy in the absence of blood circulation, this rapid and massive fluid excretion cannot be explained by any enzyme-mediated membrane-related pump mechanism. An osmotic mechanism can also be discounted. In contrast, it is in conformity with the above mentioned non-enzymatic (physicochemical) phenomenon, the phase transition of a supra-cytoskeletal gel network storing free energy in the form of non-covalent interactions.

It has been well established that both applied and endogenous electric fields can modulate neuronal activity in various preparations. In this paper, we present the effects of applied currents on spontaneous epileptiform activity in the CA1 region of the rat hippocampus. A computer-controlled system was designed to detect the spontaneous abnormal activity and then apply current pulses of programmable amplitude with monopolar electrodes in the stratum pyramidale. The epileptiform activity was generated by subperfusion of the neural tissue with an elevated potassium artificial cerebrospinal fluid (CSF) solution. Extracellular recordings showed that the interictal bursts could be fully suppressed in 90% of the slices by subthreshold currents with an average amplitude of 12.5 microA. Intracellular recordings showed that the anodic currents generated hyperpolarization of the somatic membrane thereby suppressing neuronal firing. This inhibitory effect of applied current pulses is important for the understanding of electric field effects on abnormal neuronal activity and could be an effective means of preventing the spread of epileptiform activity.

Research on the escape system of the cockroach has focused upon the role of giant interneurons in conveying information on wind stimulation from the cerci located on the abdomen to motor control centers in the thoracic ganglia. In the thoracic ganglia the ventral giant interneurons connect to a population of interganglionic interneurons referred to as type A thoracic interneurons. In this paper we have tested the type A interneurons for additional sensory inputs in the absence of ventral giant interneuron activity. We find that the cells that receive ventral giant interneuron activity are also influenced by a variety of additional sensory inputs; wind mediated activity in a pathway that descends from the head, tactile inputs from several loci, auditory stimuli and light responses. Moreover, behavioral observations indicate that at least some of these activities can alter the escape movements. The results suggest that these interneurons serve as a site of convergence for numerous types of sensory activity. They further suggest that the escape system is capable of responding to directional wind information encoded in the ventral giant interneurons in the context of a wealth of additional information.