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The ability to actively suppress, or gate, irrelevant sensory information is needed for safe and efficient walking in sensory-rich environments. Both attention and the late phase of motor preparation alter somatosensory evoked potentials (SEPs) in healthy adults. The aim of this study was to examine the effect of attention on the processing of irrelevant somatosensory information during the early phase of preparation of plantarflexion movements. Young healthy individuals received tibial nerve stimulation while electroencephalography (EEG) recorded SEPs over the Cz electrode. Three conditions were tested in both legs: 1) Rest, 2) Attend To the stimulated limb, and 3) Attend Away from the stimulated limb. In conditions 2 and 3, vibration (80 Hz) was applied over the medial soleus muscle to cue voluntary plantarflexion movements of the stimulated (Attend To) or non-stimulated leg (Attend Away). Only SEPs delivered during early preparation were averaged for statistical analysis. Results demonstrated a main effect of condition for the N40 and N70 indicating that SEP amplitudes in the Attend To condition were smaller than rest (p ≤ 0.02). For the P50, no interaction effects or main effects were found (p ≥ 0.08). There was no main effect of leg for any component measured. The results indicate that gating of irrelevant sensory information during early preparation occurs in the leg when attention is directed within the same limb. If attention alters the somatosensory stimuli from a leg movement, then directing attention may affect safe community walking.

To better understand the contributions of effort on cortical activation associated with motor tasks, healthy participants with varying capacities for isolating the control of individual finger movements performed tasks consisting of a single concurrent abduction of all digits (Easy) and paired finger abduction with digits 2 and 3 abducted together concurrently with digits 4 and 5 (Hard). Brain activity was inferred from measurement using functional magnetic resonance imaging. Effort was measured physiologically using electrodermal responses (EDR) and subjectively using the Borg scale. On average, the Borg score for the Hard task was significantly higher (p=0.007) than for the Easy task (2.9+/-1.1 vs. 1.4+/-0.7, respectively). Similarly, the average normalized peak-to-peak amplitude of the EDR was significantly higher (p=0.002) for the Hard task than for the Easy task (20.4+/-6.5% vs. 12.1+/-4.9%, respectively). The Hard task produced increases in sensorimotor network activation, including supplementary motor area, premotor, sensorimotor and parietal cortices, cerebellum and thalamus. When the imaging data were subdivided based on Borg score, there was an increase in activation and involvement of additional areas, including extrastriate and prefrontal cortices. Subdividing the data based on EDR amplitude produced greater effects including activation of the premotor and parietal cortices. These results show that the effort required for task performance influences the interpretation of fMRI data. This work establishes understanding and methodology for advancing future studies of the link between effort and motor control, and may be clinically relevant to sensorimotor recovery from neurologic injury.

Recent perceptual neuroimaging studies have shown that intermodal selective attention extracts relevant information from one modality at the expense of another at the level of unimodal sensory cortex. The present paper sought 1) to determine the effects of intermodal selective attention on primary somatosensory cortex (S1) during continuous sensorimotor transformations, 2) to investigate the interactions of spatial relationship between the target and distracter modalities on S1 and 3) to identify any potential modulators during continuous sensorimotor transformations. Functional MRI was acquired while participants (n=10) received simultaneous vibrotactile and visuospatial stimulation. In each condition, participants tracked either vibrotactile stimulation (25 Hz), applied to the right index finger with variable intensity, or a visuospatial stimulus, a centrally presented dial where the spatial position of a needle randomly moved, by applying graded force to a force sensing resistor. The distracter modality either originated from a location that was spatially related or distinct to the target that guided movement. Vibrotactile tracking resulted in decreased S1 activation relative to when it was task-irrelevant. Neither S1 activity nor tracking performance was influenced by spatial relationship. In addition the superior parietal lobe/precuneus (BA 7), inferior parietal lobe (BA 40), precentral gyrus (BA 6) and secondary visual areas (BA 18 and 19) may modulate the extraction of task-relevant information while the insula (BA 13) may do so during cases of spatial conflict. We conclude that modulation of S1 is important to the proper execution of sensory-guided movements and that sensorimotor requirements determine the mechanisms of intermodal selective attention.

Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury.

A primary feature of epilepsy is the potential for focal seizures to recruit distant structures and generalize into convulsions. Key to understanding generalization is to identify critical structures facilitating the transition from focal to generalized seizures. In kindling, development of a primary site leads progressively to secondarily generalized convulsions. In addition, subsequent kindling of a secondary site results in rapid kindling from that site, presumably because of its facilitated access to the primary kindled network. Here, we investigated the role of the piriform cortex in convulsive generalization from a secondary site kindled in the hippocampus after primary site amygdala kindling. In a necessarily complicated design, rats initially experienced forebrain commissurotomy to lateralize the experiment to one hemisphere. Then the amygdala was kindled and, 3 weeks later, it was electrically-triggered into status epilepticus, which destroyed the ipsilateral piriform cortex. This experience occurred several days before secondary site kindling of the dorsal hippocampus. In rats with complete piriform cortex loss, there was no disruption in kindling or convulsive seizure expression from the hippocampus. However, when damage also involved parts of the perirhinal, insular and entorhinal cortices, convulsive expression was blocked. Although other evidence suggests that piriform lesions affect generalization of primary site kindling, the present study shows that they do not alter secondary site kindling in the dorsal hippocampus. The additional involvement of parahippocampal cortical areas in convulsive expression suggests an important functional association between these cortical regions and the hippocampus in seizure propagation and clinical expression.

The objective was to determine if projections of single neurons to primary motor cortex preferentially terminate in several efferent zones that could form synergies for the execution of limb movements. Intracortical microstimulation was used to identify zones evoking hip flexion (HF), elbow flexion (EF), and both plantarflexion (PF) and dorsiflexion (DF) about the ankle. Histological examination showed that the zones from which some movements were evoked extended beyond the agranular cortex into granular cortex. Fluorogold, Fast blue, and propridium iodide or rhodamine-labeled dextran were injected into three of these four efferent zones in each rat. There was a virtual absence of multiple-labeled cells despite having an intermingling of different-colored cells of which 15% in frontal cortex were less than 1.2 mm away from a neighboring neuron that projected to a different efferent zone. This suggests that single neurons projecting to the motor cortex do not hard-wire specific synergies but rather project to single efferent zones in order to offer the greatest degree of freedom for the generation of movements. The distribution of ventral posterolateral and ventrolateral thalamic nucleus labeling depended on whether the injections were in granular or agranular cortex. Conversely, frontal cortex projections to motor efferent zones were made irrespective of their location in either granular or agranular cortex and thereby supporting their presumed role in the control of movements. Hindlimb motor cortex injections yielded retrograde labeling that extended into the more localised distribution of frontal cortex neurons retrogradely labeled from forelimb injections. This may allow hindlimb movements to be synchronized by forelimb movements during walking on challenging terrain.

Movement-related gating of somatosensory evoked potentials in the upper limb is restricted mainly to nerve stimulation supplying the moved limb segment. In the lower limb, this principle may not be followed. Tibial nerve (stimulation at the knee) somatosensory evoked potentials (SEPs) and soleus H reflexes exhibit quite similar patterns of modulation during movement. We hypothesised that movement-related gating of initial SEPs in the leg would be generalised from ipsilateral to contralateral leg movement and that such sensory gating would not be generalised to modalities with no functional relevance to the movement. Somatosensory, visual, and auditory evoked potentials (SEPs, VEPs, and AEPs) were recorded from scalp electrodes during unilateral passive movement. Short-latency tibial nerve SEPs, representing the first cortical components, and soleus H reflexes in both the moved leg and the stationary leg were attenuated compared to non-movement controls (p0.05). Neither VEPs nor middle latency AEPs were modulated (p0.05). We conclude that sensory gating occurs during contralateral movement. This gating is absent in other sensory modalities with no apparent functional relationship to the imposed movement.

Passive pedaling movements of the leg results in the phasic modulation of the soleus H reflex of that leg. In contrast, the H reflex of the contralateral leg is attenuated tonically. The phasic modulation of the reflex ipsilaterally can be attributed to the afferent discharge associated with the cyclic lengthening of the extensor muscles. We hypothesized that the tonic attenuation of the contralateral reflex could be explained if the afferent feedback arising from the lengthening of the biarticular muscles had an increased importance in regulating the amplitude of the contralateral reflex. To test this, the passive pedaling movements were reduced to those about either the knee or hip alone. Despite the alteration in the pattern of stretching of the biarticular muscles, the contralateral soleus H reflex was tonically attenuated during both forms of single joint movements. We suggest that the same phasic afferent discharge responsible for the modulation of the ipsilateral soleus H reflex initiates the tonic attenuation contralaterally, but that the signal undergoes a complex transformation in crossing the cord. These results do not rule out the possibility that the stretching of the biarticular muscles contributes to the attenuation of the ipsilateral soleus H reflex, which is subsequently masked by a powerful influence from the stretching of the uniarticular extensor muscles. To test this possibility, a second experiment manipulated the lengths of the muscles of the leg by altering the positions of the static joints during isolated rotation of either the knee or hip and measuring the amplitude of the ipsilateral soleus H reflex. From the results, it was clear that stretching the uniarticular extensor muscles produced the most dramatic effects. However, the stretch of the biarticular muscles yielded mild inhibitory influences if these muscles were near their maximal lengths.

Percussion of the quadriceps tendon was used to test the hypothesis that knee extensor muscle spindle discharge initiates down-regulation of the gain of the soleus H reflex. Seven subjects participated. Soleus H reflex magnitude was observed for up to 15 s, following conditioning tendon taps of 60 N or 80 N force and 10 ms or 100 ms duration, with the knee at 60° or 90° of flexion. The tap elicited quadriceps stretch reflexes in four subjects, with a mean latency of 42 ms. The major component of the conditioning of the soleus H reflex was significant attenuation of magnitude by 30–90% of controls, starting as early as 36 ms post-percussion and lasting as long as 3–8 s. The attenuation of reflex magnitude was evident, whichever combination of duration and force of tap was used. Preceding and/or following this inhibition, there was mild facilitation. Static stretch of quadriceps also significantly reduced soleus H reflex magnitude. These results support the spindle receptor origin for the gain attenuation seen during movement. The time course of the gain attenuation suggests a spinal route, by which the spindle discharge of the heteronymous extensor muscles initiates presynaptic inhibition of transmission through the reflex pathway.

Human soleus H reflexes are attenuated during passive pedalling movements. This depression occurs within 70 ms of movement onset. We hypothesized that the reflex gain would return to control values with a similar brevity following movement. However, H reflexes sampled following a slow (10 rpm) passive pedalling movement of a single leg remained below control values for the duration of a 200 ms collection period, for all four pedal positions tested. The extent of the attenuation after movement was position dependent in a manner similar to that observed during movement. This position effect was more precisely defined by sampling reflexes 200 ms post-movement at 10 pedal crank positions. Also, the full course of reflex recovery was investigated by sampling up to 8 s post-movement at four pedal positions. Reflex gain remained reduced 1–4 s post-movement, in a position dependent manner. There was a subsequent facilitation of the reflex. Thus, following a locomotor-like movement there is sustained attenuation of the soleus H reflex. The early post-movement period is likely the continued expression of movement-induced reflex inhibition while the later period may arise from descending influences consequent to the termination of movement. Presynaptic inhibition is implicated, as reflexes still showed the gain modulation when sampled while soleus was tonically contracted, both following and during the passive movement.

The gain of the H reflex attenuates during passive stepping and pedalling movements of the leg. We hypothesized that the kinematics of the movement indirectly reflect the receptor origin of this attenuation. In the first experiment, H reflexes were evoked in soleus at 26 points in the cycle of slow, passive pedalling movement of the leg and at 13 points with the leg static (the ankle was always immobilized). Maximum inhibition occurred as the leg moved through its most flexed position (P < 0.05). Inhibition observed in the static leg was also strongest at this position (P < 0.05). The increase in inhibition was gradual during flexion movement, with rapid reversal of this increase during extension. In the second experiment, the length of stretch of the vasti muscles was modelled. Variable pedal crank lengths and revolutions per minute (rpm) altered leg joint displacements and angular velocities. Equivalent rates of stretch of the vasti, achieved through different combinations of joint displacements and velocities, elicited equivalent attenuations of mean reflex magnitudes in the flexed leg. Reflex gain exponentially related to rate of stretch (R2 = 0.98 P < 0.01). The results imply that gain attenuation of this spinal sensorimotor path arises from spindle discharge in heteronymous extensor muscles of knee and/or hip, concomitant with movement.

The electrophysiological characteristics of intracellularly recorded locus coeruleus (LC) neurons in brain stem slices from DSP-4 treated animals have been compared to those from untreated controls. LC neurons from DSP-4 treated animals had action potentials and Ca2+ spikes (elicited in the presence of TTX) of significantly reduced duration compared to controls. These observations suggest that chemical axotomy with DSP-4 reduces Ca2+ conductance in neurons of the locus coeruleus.

Bimanual movement can increase activity within the stroke-affected hemisphere and may contribute to recovery in some patients. To understand how bimanual learning may aid recovery post-stroke, the present study used EEG to investigate cortical adaptations associated with short-term bimanual training and the behavioral modulations that transfer to unimanual movement in healthy individuals. Movement-related potentials (MRP) and reaction times (RT) were recorded from 10 healthy subjects during blocks of unimanual visuomotor trials before and after a bimanual training task. We hypothesized that short-term bimanual practice would induce adaptive cortical changes evident in the MRPs to movements involving a single hand. Post-training results showed that: (1) the late MRP amplitude did not change, (2) RT significantly decreased, and (3) there was a trend for the early MRP amplitude to increase. There was a strong relationship between modulation of early MRP amplitude and RT in the unimanual movement blocks before and after training. Specifically, a subgroup showed a significant decrease in RT in conjunction with a significant increase in the early MRP amplitude. Lastly, comparing later to earlier trials within the bimanual training block, task accuracy and early MRP amplitude significantly increased and (2) a positive re-afferent potential significantly decreased. Results suggest that short-term bimanual training is associated with possible transfer effects to a unimanual task reflected in changes of MRP components and RT. Furthermore, results from the bimanual training trial itself indicate that short-term bimanual training can change the level of motor preparation and sensory feedback in all subjects.

This study investigated the control of sensory inputs during the performance of an inverted-pendulum balancing task. Experiments were conducted to examine modulation of proprioceptive inputs during balance tasks of varying difficulty. It was hypothesized that proprioceptive inputs to both spinal and cortical levels would be facilitated during a challenged balance task. In contrast, during challenged balance control, results revealed task-specific facilitation of sensory inputs to the cortex and inhibition of the spinal reflex pathway. Observations of increased transmission of proprioceptive inputs to the cortex and decreased transmission at the spinal level suggest that the cortex plays an important role in challenged balance, whereas the role for the spinal stretch reflex appears to be less important.

The afferent origin of the secondary somatosensory evoked potential elicited from stimulation of the sural and tibial nerves was investigated as the limb was cooled. It was hypothesized that the peak of this potential is initiated from primary afferents in the A alpha group. We conclude that the peak of the secondary SEP arises from an afferent source whose diameter is of similar size to that of large diameter A alpha afferents.

We hypothesized that sensory input from the moving leg induces presynaptic inhibition of the soleus H reflex pathway in the contralateral stationary leg. The results showed a crossed inhibition during passive pedalling movement of the leg, which was not removed by low levels of tonic contraction of soleus in the stationary leg. The inhibition was correlated exponentially to the rate of the movement (R2 = 0.934, P < 0.05) and was not dependent on the quadrants through which the moving leg was passing. Static flexion of the stationary leg caused ipsilateral inhibition of the reflexes (t = 5.590, P < 0.05), independent of the orientations of the other leg. We concluded that sensory inflow from the moving leg induces presynaptic inhibition in the stationary leg, that a complex transformation of the sensory input in the spinal cord or brain underlies the tonic crossed inhibition and phasic ipsilateral inhibition, and that descending motor commands exert a powerful control over these sensorimotor modulatory mechanisms.

Significant movement-induced gain changes in H reflexes have been observed in soleus muscle following passive movement of the lower limb. Hypotheses from these concepts were tested on magnitudes of H reflexes in tonically contracted tibialis anterior. From eleven subjects at rates of 20 and 60 r.p.m. passive leg movement, statistically significant attenuation from controls and phasic modulation occurred. The results make more general the conclusions from soleus H reflexes. However, the functional effect should be much smaller, as tibialis anterior H reflexes are smaller compared to those in soleus.

In the present paper immunocytochemical analysis at the fluorescence microscopical level has been performed of neural cell adhesion molecule (NCAM) immunoreactivity in the adult rat tel- and diencephalon in order to further substantiate the highly selective neuronal localization of NCAM immunoreactivity, using an affinity purified rabbit antiserum recognizing homologous NCAM proteins from rat brain. Also, double immunolabelling experiments were performed with monoclonal antibodies specific for heparan sulfate related epitopes or γ -aminobutyric acid (GABA) to establish in which cell populations a colocalization existed with immunoreactive heparan sulfate proteoglycans or GABA. Within the neocortex NCAM immunoreactivity was exclusively localized to the area of the cell membrane of soma and proximal dendrites of subsets of large pyramidal nerve cells of the layer 5 of the frontoparietal cortex. Within the dorsal hippocampus, the NCAM immunoreactivity was exclusively located to the cell surface area of the pyramidal cell bodies of area CA2. Two colour immunofluorescence procedures demonstrated a colocalization of NCAM and 3G10 but not 10E4 immunoreactivities in the cell surface area of many of the NCAM-positive nerve cell bodies of these two regions. Within the thalamus, strong NCAM immunoreactivity was exclusively demonstrated at all rostrocaudal levels of the reticular thalamic nucleus. The horizontal band of NCAM immunoreactivity was not continuous, but split up into patches of NCAM immunoreactivity within groups of nerve cell bodies. When analysing the number of cells per unitary square in the rostrocaudal direction, a significant increase of positive cells was found in the rostral and middle thirds versus the caudal third of the reticular thalamic nucleus. Many of the cell bodies with NCAM immunoreactivity in their cell surface area showed cytoplasmic GABA immunoreactivity. In the three regions shown to contain NCAM immunoreactivity, proteins of the NCAM type may play a special role for the maintenance of the synaptic structure. The findings also suggest that the sulfated proteoglycans and NCAM can interact in the regulation of cell–cell interaction via adhesion. In the reticular thalamic nucleus NCAM molecules may be part of a set of cell-adhesion molecules involved in a structural organization of the nucleus, which allows it to play a key role in relating cortical maps to thalamic maps.

Evidence is provided that carbonic anhydrase-II is localized in the central nervous system to wide spread systems of oligodendrocytes and restricted astroglia populations, involving both fiber bundles and neuropil. It is suggested that CO2 formed in activated axons may, via carbonic anhydrase-II, give rise to protons controlling the excitability of surrounding neuropil. Thus, CO2 may represent an important, highly diffusible, signal in brain, involved in the tonic control of neuronal activity.

The effect of capsaicin injections into neenatal rats on the ultrastructure of the neonatal dorsal horn and on some biochemical and behavioral parameters in the adult were examined. Electron microscopic observations revealed degeneration and glial engulfment of boutons and umyelinated axons in the dorsal horn 2 and 6 h after neonatal subcuntaneous capsaicin injections. Capsaicin treatment had no effect on the activities of glutamic acid decar☐ylase and choline acetytransferase in the dorsal horn. Results of substance P measurements in the CNS showed no effect of capsicin administration on straital, hypothalamic or nigral substance P content, whereas substance P levels in the dorsal horn of teh spinal cord were reduced by half. The density of [3Hnaloxone binding sites in the dorsal horn was significantly reduced, while the affinity was not affected. Capsaicin-treated animals showed significantly increased latencies to respond to a noxious thermal stimulus in both tail-flick and hot- plate tests. The results are discussed in relation to the current concepts of the involvement of substance P and opiate systems in nociception and the potential use of neonatal capsaicin as a selective neurotoxin for the education of the spinal mechanisms of pain.

The transmitters contained in the efferent projections of the striatum were studied by producing two types of lesions: coronal hemitransections just anterior to the globus pallidus, and semi-circular knife cuts that isolated a considerable portion of the globus pallidus from the striatum to produce 'GP islands'. The levels of substance P and Met-enkephalin in the globus pallidus, entopeduncular nucleus and substantia nigra were measured after these lesions. For comparison, the effect of these lesions on glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) in some of these projection areas of the striatum was assessed. Both lesions caused similar reductions in substance P levels in each of the three striatal projection areas. In contrast, hemitransections reduced Met-enkephalin levels only in the globus pallidus. Both lesions reduced pallidal and entopeduncular GAD activity while nigral GAD activity was reduced only by the hemitransections. CAT activity was reduced in the globus pallidus by both lesions but was unaltered in the entopeduncular nucleus. However, additional experiments ruled out the existence of a striato-pallidal cholinergic projection. GAD activity and Met-enkephalin levels were significantly increased in the striatum anterior to the lesions. In contrast, CAT activity and substance P levels did not change in this region. The results support and broaden emerging view of the organization of the neurons containing the various transmitter candidates of the efferent projections of the striatum.

It is now wel recognized that there are several groups of cholinergic neurons in the basal forebrain with direct projections to various cortical regions. Immunohistochemical investigations of the distribution of the neuropeptide galanin (GAL) have shown that two of these brain areas, the medial septum and diagonal band, contained large numbers of GAL-immunoreactive neurons. In the present study, double staining techniques using antibodies raised against choline acetyltransferase (ChAT) revealed that GAL- and ChAT- like immunoreactivities are colocalized within a subpopulation of the cholinergic neurons within the medial septum and diagonal band. This colocalization of GAL- and ChAT-immunoreactivities was not seen to occur within other groups of forebrain cholinergic neurons. Immunohistochemistry carried out subsequent to injections of fluorescent retrograde tracers into the hippocampal formation revealed that both ChAT/GAL- and ChAT-containing neurons project to the hippocampal formation. The question of GAL as a modulator of cholinergic transmission in this projection is discussed.

A projection from the globus pallidus (GP) to the striatum in the rat was demonstrated by a retrograde tracer technique. After injections of lectin-conjugated horseradish peroxidase (WGA-HRP) which were wholly confined to the striatum, the GP exhibited reaction product characteristic of both retrograde and anterograde transport of marker. Electron microscopic examination of the GP confirmed the presence of both perikaryal and terminal labeling. Coinjection of kainic acid and WGA-HRP into the striatum blocked the appearance of anterograde label in the GP but the retrogradely labeled pallidal neurons remained visible.

Adenosine deaminase (ADA) was localized within several types of neurons within the septum and in septal efferent projections to the habenula by immunohistochemical, biochemical, retrograde tracing and lesion methods. Numerous ADA-immunoreactive (ADA-IR) neurons were observed in the septofimbrial nucleus, the triangular septal nucleus and the bed nucleus of the anterior commissure, while considerably fewer numbers were seen in the lateral septal area. Based on their size, shape and dendritic features, 4 morphologically distinct types of ADA-IR neurons were recognized in these septal structures. In addition, fine, non-varicose, ADA-IR fibers appeared to emanate from the postcommissural cell groups and these coalesced within the stria medullaris, continued caudally within this fiber bundle, and gave rise to a dense field of very fine immunoreactive elements within a restricted zone of the dorsal half of the medial habenula. Comparisons of the habenular localization of ADA-IR and enkephalin-IR elements showed that fibers labelled for either ADA or enkephalin occupied distinct, non-overlapping regions within the dorsal half of the medial habenula. After injections of Fluoro-gold (FG) into the medial habenula, the majority of ADA-IR neurons in the septofimbrial nucleus, triangular septal nucleus, and the bed nucleus of the anterior commissure were retrogradely labelled with this fluorescent tracer, whereas no ADA-positive FG-labelled neurons were observed in the lateral septal region. Unilateral transections of the stria medullaris caused substantial depletions of ADA-immunoreactivity and reduced enzymatically determined ADA activity by up to 80% in the medial habenula on the lesioned compared with the contralateral control side. These results demonstrate that ADA-IR neurons in the septum are heterogeneously distributed and that populations of positive neurons within the postcommissural septal nuclei give rise to dense, focal projections to the medial habenula. These projections appear to be restricted to a portion of the medial habenula known to contain substance P-IR neurons and are subregionally segregated from enkephalin-positive septohabenular projections ending within this same portion. In addition to pointing out a unique capacity for adenosine catabolism within some septal neurons, possibly related to purinergic neuromodulation, the results indicate the utility of ADA-immunohistochemistry for the delineation of anatomical relationships between the septum and the medial habenula.

Immunohistochemical, neuroanatomical and lesion methods were used to investigate the projections of adenosine deaminase immunoreactive (ADA-IR) neurons in the striatum (caudate/putamen) and hypothalamus to the substantia nigra (SN). Striatal ADA-IR neurons were distributed within two zones; anteriorly in the medial and ventromedial extreme of the head and body of the striatum, and posteriorly in the tail of the striatum. The posterior hypothalamus contained ADA-positive neurons which were confined to the tuberomammillary nucleus (TM). The SN was devoid of ADA-positive neurons, but contained two distinct types of ADA-IR fiber terminations. One type was confined to bands located at the ventrolateral and dorsomedial borders of the pars reticulata and consisted of fine puncta. The other type was distributed throughout the SN and consisted of long, beaded fibers. Injections of the retrograde tracer Fluoro-gold (FG) into the SN gave rise to FG-labelling of significant numbers of ADA-IR neurons in both the striatum and TM. Medical SN injections preferentially labelled ADA-IR neurons in the anterior striatum and lateral SN injections labelled posterior ADA-IR striatal neurons. Kainic acid lesions of the anterior medial striatum selectively abolished the punctate ADA-IR band in the medial SN and left the long, ADA-IR nigral fibers in an apparently hypertrophied state. Despite depletion of ADA-IR neurons in the striatum by kainic acid, ADA activity increased significantly at striatal lesion sites. The results suggest that the SN receives two topographically segregated fine terminal fields from striatal ADA-IR neurons, and a substantial innervation from ADA-IR neurons in the TM as well. These findings add to the heterogeneous chemical composition of nigral afferents and are discussed in the context of adenosine neuromodulatory mechanisms in the striatonigral system.