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An abstract of the article "Crossmodal Audio-Visual Interactions in the Primary Visual Cortex of the Visually Deprived Cat: A Physiological and Anatomical Study," by M. V. Sanchez-Vives is presented.

The subiculum is a pivotal structure located in the hippocampal formation that receives inputs from grid and place cells and that mediates the output from the hippocampus to cortical and sub-cortical areas. Previous studies have demonstrated the existence of boundary vector cells (BVC) in the subiculum, as well as exceptional stability during recordings conducted in the dark, suggesting that the subiculum is involved in the coding of allocentric cues and also in path integration. In order to better understand the role of the subiculum in spatial processing and the coding of external cues, we recorded subicular units in freely moving rats while performing two experiments: the "size experiment" in which we modified the arena size, and the "barrier experiment" in which we inserted new barriers in a familiar open field thus dividing the enclosure into four comparable sub-chambers. We hypothesized that if physical boundaries were deterministic of the firing of subicular units a strong spatial replication pattern would be found in most spatially modulated units. In contrast, our results demonstrate heterogeneous space coding by different cell types: place cells, barrier-related units and BVC. We also found units characterized by narrow spike waveforms, most likely belonging to axonal recordings, that showed grid-like patterns. Our data indicate that the subiculum codes space in a flexible manner, and that it is involved in the processing of allocentric information, external cues and path integration, thus broadly supporting spatial navigation., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

The function of sleep remained one of largest enigmas of neuroscience for most of the 20th century. However in recent years different evidence has accumulated in support of a critical role of sleep on functions such as replay and memory consolidation. In particular slow wave sleep, and its underlying corticothalamocortical activity, slow oscillations, could be critical not only for memory but also for the maintenance of the brain's structural and func- tional connectivity. In this article we ask: why slow oscillations? To answer this question we put forward the idea that slow oscillations are the default activity of the cortical network based on both experimental and theoretical evidence. We go on to discuss why slow oscillations emerge from the cortical circuits and what are the dynamic advantages of this activity pattern, such as the resilience to perturbances and the facilitation of transitions between a disconnected (e.g. deep sleep) brain and a connected, awake brain.

Blind individuals often demonstrate enhanced non-visual perceptual abilities. Neuroimaging and transcranial magnetic stimulation experiments have suggested that computations carried out in the occipital cortex may underlie these enhanced somatosensory or auditory performances. Thus, cortical areas that are dedicated to the analysis of the visual scene may, in the blind, acquire the capacity to participate in other sensory processing. However, the neural substrate that underlies this transfer of function is not fully characterized. Here we studied the synaptic and anatomical basis of this phenomenon in cats that were visually deprived by dark rearing, either early visually deprived after birth (EVD), or late visually deprived after the end of the critical period (LVD); data were compared with those obtained in normally reared cats (controls). The presence of synaptic and spike responses to auditory stimulation was examined by means of intracellular recordings in area 17 and the border between areas 17 and 18. While none of the cells recorded in control and LVD cats showed responses to sound, 14% of the cells recorded in EVD cats showed both subthreshold synaptic responses and suprathreshold spike responses to auditory stimuli. Synaptic responses were of small amplitude, but well time-locked to the stimuli and had an average latency of 30+/-12ms. In an attempt to identify the origin of the inputs carrying auditory information to the visual cortex, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling examined in the cortex and thalamus. No significant retrograde labeling was found in auditory cortical areas. However, the proportion of neurons projecting from supragranular layers of the posteromedial and posterolateral parts of the lateral suprasylvian region to V1 was higher than that in control cats. Retrograde labeling in the lateral geniculate nucleus showed no difference in the total number of neurons between control and visually deprived cats, but there was a higher proportion of labeling in C-laminae in deprived cats. Labeled cells were not found in the medial geniculate nucleus, a thalamic relay for auditory information, in either control or visually deprived cats. Finally, immunohistochemistry of the visual cortex of deprived cats revealed a striking decrease in pavalbumin- and calretinin-positive neurons, the functional implications of which we discuss.

Pattern matching is a simple method for studying the properties of information sources based on individual sequences (Wyner et al 1998 IEEE Trans. Inf. Theory 44 2045-56). In particular, the normalized Lempel-Ziv complexity (Lempel and Ziv 1976 IEEE Trans. Inf. Theory 22 75-88), which measures the rate of generation of new patterns along a sequence, is closely related to such important source properties as entropy and information compression ratio. We make use of this concept to characterize the responses of neurons of the primary visual cortex to different kinds of stimulus, including visual stimulation (sinusoidal drifting gratings) and intracellular current injections (sinusoidal and random currents), under two conditions (in vivo and in vitro preparations). Specifically, we digitize the neuronal discharges with several encoding techniques and employ the complexity curves of the resulting discrete signals as fingerprints of the stimuli ensembles. Our results show, for example, that if the neural discharges are encoded with a particular one-parameter method ('interspike time coding'), the normalized complexity remains constant within some classes of stimuli for a wide range of the parameter. Such constant values of the normalized complexity allow then the differentiation of the stimuli classes. With other encodings (e.g. 'bin coding'), the whole complexity curve is needed to achieve this goal. In any case, it turns out that the normalized complexity of the neural discharges in vivo are higher (and hence carry more information in the sense of Shannon) than in vitro for the same kind of stimulus.

In a previous paper (Proceedings of the World Congress on Neuroinformatics (2001)) the authors applied the so-called Lempel-Ziv complexity to study neural discharges (spike trains) from an information-theoretical point of view. Along with other results, it is shown there that this concept of complexity allows to characterize the responses of primary visual cortical neurons to both random and periodic stimuli. To this aim we modeled the neurons as information sources and the spike trains as messages generated by them. In this paper, we study further consequences of this mathematical approach, this time concerning the number of states of such neuronal information sources. In this context, the state of an information source means an internal degree of freedom (or parameter) which allows outputs with more general stochastic properties, since symbol generation probabilities at every time step may additionally depend on the value of the current state of the neuron. Furthermore, if the source is ergodic and Markovian, the number of states is directly related to the stochastic dependence lag of the source and provides a measure of the autocorrelation of its messages. Here, we find that the number of states of the neurons depends on the kind of stimulus and the type of preparation ( in vivo versus in vitro recordings), thus providing another way of differentiating neuronal responses. In particular, we observed that (for the encoding methods considered) in vitro sources have a higher lag than in vivo sources for periodic stimuli. This supports the conclusion put forward in the paper mentioned above that, for the same kind of stimulus, in vivo responses are more random (hence, more difficult to compress) than in vitro responses and, consequently, the former transmit more information than the latter.

The neocortex generates periods of recurrent activity, such as the slow (0.1-0.5 Hz) oscillation during slow-wave sleep. Here we demonstrate that slices of ferret neocortex maintained in vitro generate this slow (< 1 Hz) rhythm when placed in a bathing medium that mimics the extracellular ionic composition in situ. This slow oscillation seems to be initiated in layer 5 as an excitatory interaction between pyramidal neurons and propagates through the neocortex. Our results demonstrate that the cerebral cortex generates an 'up' or depolarized state through recurrent excitation that is regulated by inhibitory networks, thereby allowing local cortical circuits to enter into temporarily activated and self-maintained excitatory states. The spontaneous generation and failure of this self-excited state may account for the generation of a subset of cortical rhythms during sleep.

The cellular mechanisms of spike-frequency adaptation during prolonged discharges and of the slow afterhyperpolarization (AHP) that follows, as occur in vivo with contrast adaptation, were investigated with intracellular recordings of cortical neurons in slices of ferret primary visual cortex. Intracellular injection of 2 Hz sinusoidal or constant currents for 20 sec resulted in a slow (tau = 1-10 sec) spike-frequency adaptation, the degree of which varied widely among neurons. Reducing either [Ca(2+)](o) or [Na(+)](o) reduced the rate of spike-frequency adaptation. After the prolonged discharge was a slow (12-75 sec) AHP that was associated with an increase in membrane conductance and a rightward shift in the discharge frequency versus injected current relationship. The reversal potential of the slow AHP was sensitive to changes in [K(+)](o), indicating that it was mediated by a K(+) current. Blockade of transmembrane Ca(2+) conductances did not reduce the slow AHP. In contrast, reductions of [Na(+)](o) reduced the slow AHP, even in the presence of pronounced Ca(2+) spikes. We suggest that the activation of Na(+)-activated and Ca(2+)-activated K(+) currents plays an important role in prolonged spike-frequency adaptation and therefore may contribute to contrast adaptation and other forms of adaptation in the visual system in vivo.

Contrast adaptation is a psychophysical phenomenon, the neuronal bases of which reside largely in the primary visual cortex. The cellular mechanisms of contrast adaptation were investigated in the cat primary visual cortex in vivo through intracellular recording and current injections. Visual cortex cells, and to a much less extent, dorsal lateral geniculate nucleus (dLGN) neurons, exhibited a reduction in firing rate during prolonged presentations of a high-contrast visual stimulus, a process we termed high-contrast adaptation. In a majority of cortical and dLGN cells, the period of adaptation to high contrast was followed by a prolonged (5-80 sec) period of reduced responsiveness to a low-contrast stimulus (postadaptation suppression), an effect that was associated, and positively correlated, with a hyperpolarization of the membrane potential and an increase in apparent membrane conductance. In simple cells, the period of postadaptation suppression was not consistently associated with a decrease in the grating modulated component of the evoked synaptic barrages (the F1 component). The generation of the hyperpolarization appears to be at least partially intrinsic to the recorded cells, because the induction of neuronal activity with the intracellular injection of current resulted in both a hyperpolarization of the membrane potential and a decrease in the spike response to either current injections or visual stimuli. Conversely, high-contrast visual stimulation could suppress the response to low-intensity sinusoidal current injection. We conclude that control of the membrane potential by intrinsic neuronal mechanisms contributes importantly to the adaptation of neuronal responsiveness to varying levels of contrast. This feedback mechanism, internal to cortical neurons, provides them with the ability to continually adjust their responsiveness as a function of their history of synaptic and action potential activity.

Perigeniculate neurons form an interactive sheet of cells that inhibit one another as well as thalamocortical neurons in the dorsal lateral geniculate nucleus (LGNd). The inhibitory influence of the GABAergic neurons of the perigeniculate nucleus (PGN) onto other PGN neurons was examined with intracellular recordings in vitro. Intracellular recordings from PGN neurons during the generation of spindle waves revealed barrages of EPSPs and IPSPs. The excitation of local regions of the PGN with the local application of glutamate resulted in activation of IPSPs in neighboring PGN neurons. These IPSPs displayed an average reversal potential of -77 mV and were blocked by application of bicuculline methiodide or picrotoxin, indicating that they are mediated by GABAA receptors. In the presence of GABAA receptor blockade, the activation of PGN neurons with glutamate could result in slow IPSPs that were mediated by GABAB receptors in a subset (40%) of cells. Similarly, application of specific agonists muscimol and baclofen demonstrated that PGN neurons possess both functional GABAA and GABAB receptors. Examination of the axon arbors of biocytin-filled PGN neurons often revealed the presence of beaded axon collaterals within the PGN, suggesting that this may be an anatomical substrate for PGN to PGN inhibition. Functionally, activation of inhibition between PGN neurons could result in a shortening or a complete abolition of the low threshold Ca2+ spike or an inhibition of tonic discharge. We suggest that the mutual inhibition between PGN neurons forms a mechanism by which the excitability of these cells is tightly controlled. The activation of a point within the PGN may result in the inhibition of neighboring PGN neurons. This may be reflected in the LGNd as a center of inhibition surrounded by an annulus of disinhibition, thus forming a "center-surround" mechanism for thalamic function.

The properties of the inhibitory influence of neurons in the perigeniculate (PGN) nucleus on thalamocortical cells were examined with intracellular recordings in the ferret geniculate slice maintained in vitro. Activation of PGN neurons with the local application of glutamate caused IPSPs in thalamocortical neurons that were mediated by both GABAA and GABAB receptors, as well as the activation of spindle waves. With low intensity stimulation of the PGN, local application of bicuculline to the dorsal lateral geniculate nucleus (LGNd) strongly inhibited evoked and spindle-associated IPSPs, indicating that these are largely mediated by GABAA receptors. The generation of GABAB receptor-mediated IPSPs in thalamocortical cells that were large enough to generate rebound low threshold Ca2+ spikes required substantially increased activation of the PGN with glutamate. The activation of synchronous bicuculline-induced slowed oscillations in thalamocortical neurons required the block of GABAA receptors in the LGNd as well as in the PGN. These results indicate that bursts of action potentials in PGN neurons can result in the activation of both GABAA and GABAB receptors in thalamocortical neurons, with the strong activation of GABAB receptors requiring an intense, simultaneous discharge of a number of PGN neurons. Functionally, these results suggest that PGN neurons inhibit thalamocortical cells preferentially through the activation of GABAA receptors, although the strong activation of GABAB receptors may occur under pathological conditions and contribute to the generation of abnormal, synchronous slow oscillations.

The inhibitory gamma-aminobutyric acid-containing (GABAergic) neurons of the thalamic reticular and perigeniculate nuclei are involved in the generation of normal and abnormal synchronized activity in thalamocortical networks. An important factor controlling the generation of activity in this system is the amplitude and duration of inhibitory postsynaptic potentials (IPSPs) in thalamocortical cells, which depend on the pattern of activity generated in thalamic reticular and perigeniculate cells. Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus: Low-frequency tonic discharge resulted in small-amplitude IPSPs mediated by GABAA receptors, burst firing resulted in large-amplitude GABAA IPSPs, and prolonged burst firing activated IPSPs mediated by GABAA and GABAB receptors. These functional properties of GABAergic inhibition can reconfigure the operations of thalamocortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures.

The ferret dorsal lateral geniculate nucleus (LGNd) contains interneurons within the interlaminar zones situated between the laminae corresponding to the ipsi- and contralateral eyes. We found that a subset of these neurons exhibits electrophysiological properties similar to those previously reported for perigeniculate (PGN) neurons, including the generation of rhythmic sequences of rebound low-threshold Ca2+ spikes at a frequency of 1-4 Hz after the intracellular injection of a hyperpolarizing current pulse. These "PGN-like" interlaminar interneurons innervated restricted regions of the A-laminae, inhibited thalamocortical cells through GABAA, and perhaps GABAB, receptors, and were excited by axon collaterals from thalamocortical cells. This reciprocal relationship is identical to that formed by PGN cells and allowed the PGN-like interlaminar neurons to participate in the generation of spindle waves and other network oscillations. Pharmacologically, PGN-like interlaminar interneurons were also similar to PGN neurons: both generated a prolonged depolarization in response to the local application of serotonin, 1S,3R-ACPD, and CCK8S, and a rapid depolarization followed by a more prolonged hyperpolarization in response to acetylcholine. Examination of parvalbumin and calbindin staining in the ferret LGNd revealed that both PGN and a subset of interlaminar neurons were parvalbumin-positive. In contrast, calbindin-positive cells were relatively absent in the PGN and sparsely present in the interlaminar zones, but were numerous in the A and C laminae. Our results indicate that the interlaminar zone in between laminae A and A1 and A1 and C in the ferret LGNd possesses a cell type that is electrophysiologically, pharmacologically, anatomically, immunocytochemically, and functionally similar to neurons in the PGN.

IAHP is a calcium dependent potassium current that underlies slow afterhyperpolarizations following action potentials in bullfrog sympathetic ganglion neurons. The decay rate of IAHP increases with increasing calcium loads. This effect was found not to be due to mobilization on intracellular calcium from ryanodine and caffeine sensitive stores. The relation is not affected by ryanodine at concentrations that block mobilization in the presence of caffeine, a drug that enhances mobilization of those stores. Nor does the relation seem to be due to a reduction of the driving force of the Na/Ca exchange process. The relation between decay rate and calcium load persists when Na+ is replaced by Li+. Our results suggest that Na/Ca exchange and mobilization of intracellular calcium normally have little influence in determining the time course of IAHP in these neurons.