Functional organization of local neuronal networks in the cat neocortex. Dependence on the food motivation

The multiple unit activity (MUA) from clusters of adjacent neurones in deep layers of the frontal and motor cortex was recorded in alert cats with different levels of alimentary motivation. Up to 7 spike trains were selected from the MUA. Neurones in the local circuits could be divided into 2 groups: large neurones with prevailing divergent characteristics, and small neurones with prevailing convergent characteristics. A 24-hour food deprivation altered the cross-correlation interneuronal connections with a time delay within the range of 2 to 100 ms.     

Self-organization of orientation sensitive cells in the striate cortex

A nerve net model for the visual cortex of higher vertebrates is presented. A simple learning procedure is shown to be sufficient for the organization of some essential functional properties of single units. The rather special assumptions usually made in the literature regarding preorganization of the visual cortex are thereby avoided. The model consists of 338 neurones forming a sheet analogous to the cortex. The neurones are connected randomly to a retina of 19 cells. Nine different stimuli in the form of light bars were applied. The afferent connections were modified according to a mechanism of synaptic training. After twenty presentations of all the stimuli individual cortical neurones became sensitive to only one orientation. Neurones with the same or similar orientation sensitivity tended to appear in clusters, which are analogous to cortical columns. The system was shown to be insensitive to a background of disturbing input excitations during learning. After learning it was able to repair small defects introduced into the wiring and was relatively insensitive to stimuli not used during training.     

The interrelations between neurons of the amygdala and hypothalamus during conditioning with selection of food reinforcement quality in cats

Three cats were subjected to appetitive instrumental conditioning to light by the method of the "active choice" of the reinforcement quality. The short-delayed conditioned bar-pressings were reinforced by bread-meat mixture and the delayed response by meat. The animals differed in behavior strategy: two animals preferred bar-pressing with long delay (the so-called "self-control" group) and one animal preferred bar-pressing with short delay (the so-called "impulsive" group). The multiunit activity of the basolateral amygdala and nucleus lateralis of the hypothalamus was recorded through chronically implanted nichrome wire semimicroelecrodes. The interactions between the neighboring neurons in the lateral hypothalamus and basolateral amygdala (within the local neuronal network) and between the neurons of the basolateral amygdala and lateral hypothalamus (distributed neuronal networks in the direction amygdala--hypothalamus and vice versa) were evaluated by means of statistical crosscorrelation analysis of spike trains. The crosscorrelational interneuronal connections in the delay range of 0-100 ms were examined. It was shown that the number of crosscorrelations between the discharges on neurons both in the local networks of basolateral amygdala and distributed networks was significantly higher in "impulsive" cats. In both groups of animals, the percentage of crosscorrelations between neighbouring neurons in the local networks of the lateral hypothalamus was similar. We suggest that the local networks of the basolateral amygdala and amygdalar-hypothalamic distributed neuronal networks are involved in the system of brain structures which determine the individual features of animal behavior.     

Extended difference-of-Gaussians model incorporating cortical feedback for relay cells in the lateral geniculate nucleus of cat

A striking feature of the organization of the early visual pathway is the significant feedback from primary visual cortex to cells in the dorsal lateral geniculate nucleus (LGN). Despite numerous experimental and modeling studies, the functional role for this feedback remains elusive. We present a new firing-rate-based model for LGN relay cells in cat, explicitly accounting for thalamocortical loop effects. The established DOG model, here assumed to account for the spatial aspects of the feedforward processing of visual stimuli, is extended to incorporate the influence of thalamocortical loops including a full set of orientation-selective cortical cell populations. Assuming a phase-reversed push-pull arrangement of ON and OFF cortical feedback as seen experimentally, this extended DOG (eDOG) model exhibits linear firing properties despite non-linear firing characteristics of the corticothalamic cells. The spatiotemporal receptive field of the eDOG model has a simple algebraic structure in Fourier space, while the real-space receptive field, as well as responses to visual stimuli, are found by evaluation of an integral. As an example application we use the eDOG model to study effects of cortical feedback on responses to flashing circular spots and patch-grating stimuli and find that the eDOG model can qualitatively account for experimental findings.     

Neuromediator sensitivity of neurons of the reticular formation and orbital cortex in hungry and satiated rabbits

In conditions of stereotaxic fixation, noradrenaline microionophoresis and stimulation of the lateral hypothalamus acted in the same sense on impulse activity of 35 and 37% of the neurones in the reticular formation of satiated rabbits, in joint action increasing the number of cells with distribution of intervals characteristic of alimentary motivational excitation. Microionophoresis of acetylcholine to the neurones of the orbital cortex in freely behaving rabbits reshaped the impulse activity of 57% of cells in accordance with the pattern of discharge activity characteristic of alimentary motivational excitation. Such excitation, natural as well as artificially evoked, widens polychemical properties of the neurones of the reticular formation and, on the contrary, narrows polychemical properties of the nerve cells of the orbital cortex.     

Changes in the cholinosensitivity of sensomotor cortex neurons during conditioned reflex extinction]

Characteristics of neuronal responses of the sensorimotor cortex to ionophoretically administered neuromediators (acetylcholine, L-glutamate) were studied in rabbit in the course of extinction of conditioned defensive reflex. In the majority of neurones the extinction of the conditioned reflex is accompanied by a drop of cholinosensitivity. In a number of neurones the extinction of reflexes either does not change the reaction to acetylcholine, or enhances it. The analysis of these reactions permits to assume the existence of a group of neurones directly involved in the formation, fixation and storage of the temporary connection.     

Clustered organization of neurons with similar extra-receptive field properties in the primary visual cortex

The primary visual cortex is organized into clusters of cells having similar classical receptive field (CRF) properties. Nonclassical, extra-receptive fields (ERFs) can either inhibit or facilitate the response elicited by stimulation within the CRF. Here, we report that in the primary visual cortex of cat, neurons with similar inhibitory or facilitatory ERF properties are also grouped into clusters. These clusters are randomly distributed in all cortical layers, with no detectable relationship with orientation and ocular dominance columns. This functional organization of neurons with respect to ERF properties may allow an efficient processing of global visual information.     

Effect of the enkephalin derivative DAGO on neuronal behavior and activity in the neocortex and hippocampus of rabbits during the acquisition of conditioned defense and inhibitory reflexes

After subcutaneous injection of 25 mkg/kg morphine-like opiate--DAGO a decrease was observed of probabilities of rabbits movements at light flashes--defensive reflex signal. The level of the background neuronal impulse activity became gradually lower in the sensorimotor cortex and the hippocampus and did not change in the visual cortex. Decrease and restoration of responses to the reinforcing stimulus (electrocutaneous limb stimulation) in all studied cortical zones proceeded in one direction while there were significant differences in dynamics of responses to inhibitory and reinforced light flashes depending on the studied cortical zone and biological significance of the stimulus. Appearance is discussed of particular characteristics of neurones systemic organization during learning at change of reinforcement properties under the influence of the studied substance, as well as similarity of some features of mechanisms of internal inhibition elaboration in a defensive situation and of properties of positive reinforcement.     

The role of the thalamic ventrolateral nucleus in the cortical effect on the activity of vestibular neurons

Electrocoagulation of lateral vestibular nucleus (NVL) reduces inhibitory effect of the motor and somatosensory areas and enhances the inhibitory effect of limbic, vestibular, and orbital cortical areas. Facilitating effect was enhanced by electrostimulation of the motor area and reduced by the stimulation of other cortical areas. Following the coagulation of the NVL, the ascending afferent flow to the cortex seems to be reduced. This results in diminishing of the cortical neurones tone and readjusts the descending influences upon the NVL neurones activity.     

Organization of neocortical neuronal networks

Multiple unit activity in deep layers of the frontal and motor cortices was recorded by chronically implanted semimicroelectrodes in waking cats with different levels of food motivation. From four to seven neuronal spike trains were selected from the recorded multiunit activity. Interactions between neighbouring neurons in the motor and frontal areas of the neocortex (within the local neuronal networks) and between the neurons of these areas (distributed neuronal networks) were estimated by means of statistical crosscorrelation analysis of spike trains within the range of delays from 0 to 100 ms. Neurons in the local networks were divided in two subgroups: the neurons with higher spike amplitudes with the dominance of divergent connections and neurons with lower spike amplitudes with the dominance of convergent connections. Strong monosynaptic connections (discharges with a delay of less than 2 ms) between the neurons with high- and low-amplitude spikes formed the background of the local networks. Connections between low-amplitude neurons in the frontal cortex and high-amplitude neurons in the motor cortex dominated in the distributed networks. A 24-hour food deprivation predominantly altered the late interneuronal crosscorrelations with time delays within the range of 2-100 ms in both local and distributed networks.     

Effect of GABA on a temporary connection in a neuronal population of the sensorimotor cortex in rabbits

Evoked activity of sensorimotor cortical neurones in response to stimulation of the pyramidal tract, medial lemniscus and reticular nucleus of the midbrain tegmentum; driving reaction of cortical neurones at stimulation of these brain structures of growing frequency, and conditioned reflexes elaborated by combination of direct stimulation of the sensorimotor cortex and electrocutaneous stimulation were studied in awake nonimmobilized rabbits. Application to the cortex of GABA solutions of low concentration (less than or equal to 1%) emphasizes the evoked neuronal responses, facilitates the appearance of driving reaction and contributes to the manifestation of the temporary connection. Application of GABA solutions of higher concentration (greater than 2%) leads to opposite effects. Positive correlation is found between electrical and behavioural phenomena. The described experimental approach may be used for analysis of various types of influences on temporary connection formation.     

Semantic memory and the brain: structure and processes

Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information.     

Spatial principle of organization of specific afferent projections and generation of evoked potentials in the somatosensory cortex

Here we investigate the functional organization of structures involved in sensory analysis in a restricted region of a cortical projection area. We have shown that stimulation of somatosensory areas I and II (SI and SII) may block an afferent volley at the level of the thalamic relay nucleus, and that SII may be selectively blocked by stimulation of SI. Also definite somatosensory connections have been demonstrated between SII, SI, and the motor cortex. We suggest that common mechanisms underlie the generation of focal reactions in projection areas of the cortex induced by stimulation of various structures. The properties of two groups of neurones from area SII are described: those having a short latency and receiving direct projections from the thalamic relay nucleus, and those of long latent period with a well-marked convergence, and reacting to stimulation of various afferent pathways. It is suggested that each path to a local point of a cortical projection areas terminates with its relay element. The signal is then directed to a common intracortical system of neurones where signals from various sources occurs (afferent, interhemispherical, subcortico-cortical, and intracortical) converge and interact. All groups of neurones are involved in the formation of the common components of evoked potentials.Presented to the All-Union Symposium: "Electrical responses of the cerebral cortex to afferent stimuli," Kiev, October, 1969.Institute of Normal and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 2, pp. 155–165, March–April, 1970.     

Convergence and divergence are mostly reciprocated properties of the connections in the network of cortical areas

Cognition is based on the integrated functioning of hierarchically organized cortical processing streams in a manner yet to be clarified. Because integration fundamentally depends on convergence and the complementary notion of divergence of the neuronal connections, we analysed integration by measuring the degree of convergence/divergence through the connections in the network of cortical areas. By introducing a new index, we explored the complementary convergent and divergent nature of connectional reciprocity and delineated the backward and forward cortical sub-networks for the first time. Integrative properties of the areas defined by the degree of convergence/divergence through their afferents and efferents exhibited distinctive characteristics at different levels of the cortical hierarchy. Areas previously identified as hubs exhibit information bottleneck properties. Cortical networks largely deviate from random graphs where convergence and divergence are balanced at low reciprocity level. In the cortex, which is dominated by reciprocal connections, balance appears only by further increasing the number of reciprocal connections. The results point to the decisive role of the optimal number and placement of reciprocal connections in large-scale cortical integration. Our findings also facilitate understanding of the functional interactions between the cortical areas and the information flow or its equivalents in highly recurrent natural and artificial networks.     

Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain

The distribution of endothelin mRNA and immunoreactivity in the human brain was investigated using the technique of in situ hybridization and immunocytochemistry. Cryostat sections from 22 cases of neurologically normal adult human brain, collected 3-7 h post-mortem were hybridized with 35S-labelled complementary (c)RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization with all three cRNA probes revealed labelled neuronal cell bodies in laminae III-VI of the parietal, temporal and frontal cortices. Labelled cells were also seen, scattered throughout the para- and periventricular, supraoptic and lateral hypothalamic nuclei, the caudate nucleus, amygdala, hippocampus, basal nucleus of Meynert, substantia nigra, raphe nuclei, Purkinje cell layer of the cerebellum and in the dorsal motor nuclei of the vagus of the medulla oblongata. The distribution of neurones immunoreactive to endothelin was similar to that of endothelin mRNA, although fewer immunoreactive cells throughout the brain, were noted. Immunoreactive fibres were present mainly in the cortex and hypothalamus, and to a lesser extent in the brain stem. Combined in situ hybridization and immunocytochemistry on the same section revealed the presence of endothelin-1 mRNA and immunoreactivity in the same cortical neuronal cell. Colocalisation studies in the cortex revealed endothelin-1 mRNA and immunoreactivity in a number of cells which also expressed neuropeptide Y mRNA and immunoreactivity. In the hypothalamus and basal nucleus of Meynert endothelin immunoreactivity was colocalised to a subset of neurophysin- and galanin-immunoreactive cell bodies respectively. Endothelin mRNA and immunoreactivity was also seen in some blood vessel endothelial cells. The findings of endothelin mRNAs and immunoreactivity in heterogenous neuronal populations further emphasises the potential role of endothelin as a neuropeptide, probably having diverse actions in the nervous system of man.     

Reciprocal inhibition and slow calcium decay in perigeniculate interneurons explain changes of spontaneous firing of thalamic cells caused by cortical inactivation

The role of cortical feedback in the thalamocortical processing loop has been extensively investigated over the last decades. With an exception of several cases, these searches focused on the cortical feedback exerted onto thalamo-cortical relay (TC) cells of the dorsal lateral geniculate nucleus (LGN). In a previous, physiological study, we showed in the cat visual system that cessation of cortical input, despite decrease of spontaneous activity of TC cells, increased spontaneous firing of their recurrent inhibitory interneurons located in the perigeniculate nucleus (PGN). To identify mechanisms underlying such functional changes we conducted a modeling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered six network topologies of the retino-geniculo-cortical system. All models were robust against changes of axonal delays except for the delay between the LGN feed-forward interneuron and the TC cell. The best representation of physiological results was obtained with models containing reciprocally connected PGN cells driven by the cortex and with relatively slow decay of intracellular calcium. This strongly indicates that the thalamic reticular nucleus plays an essential role in the cortical influence over thalamo-cortical relay cells while the thalamic feed-forward interneurons are not essential in this process. Further, we suggest that the dependence of the activity of PGN cells on the rate of calcium removal can be one of the key factors determining individual cell response to elimination of cortical input.     

Nitric oxide synthase and interferon-gamma receptor immunoreactivities in relation to ascending spinal pathways to thalamus,hypothalamus, and the periaqueductal grey in the rat

The retrograde tracer fluoro-gold was injected into the periaqueductal grey, thalamus or hypothalamus, and spinal cord sections were processed for neuronal nitric oxide synthase (nNOS) immunohistochemistry to investigate the relationships of nNOS immunoreactive, and spinomesencephalic, spinothalamic and spinohypothalamic projection neurones. In addition, in the lateral spinal nucleus the relationship between spinomesencephalic, -thalamic and -hypothalamic projection neurones, and nNOS and interferon-gamma receptor immunoreactive structures was investigated at the lumbar level. No single retrogradely labelled spinomesencephalic, -thalamic or -hypothalamic neurone showed nNOS immunoreactivity. In the lateral spinal nucleus, however, many fluoro-gold-labelled neurones were closely apposed by both nNOS and interferon-gamma receptor immunoreactive structures, especially prominent in the hypothalamic injection cases. This study gave no evidence for nNOS immunoreactivity in spinal neurones projecting to the periaqueductal grey, thalamus or hypothalamus, but suggests that in the lateral spinal nucleus such neurones are contacted by both nNOS- and interferon-gamma receptor-containing axon terminals.     

Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.

Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.     

Nitric oxide synthase and interferon-gamma receptor immunoreactivities in relation to ascending spinal pathways to thalamus, hypothalamus, and the periaqueductal grey in the rat

The retrograde tracer fluoro-gold was injected into the periaqueductal grey, thalamus or hypothalamus, and spinal cord sections were processed for neuronal nitric oxide synthase (nNOS) immunohistochemistry to investigate the relationships of nNOS immunoreactive, and spinomesencephalic, spinothalamic and spinohypothalamic projection neurones. In addition, in the lateral spinal nucleus the relationship between spinomesencephalic, -thalamic and -hypothalamic projection neurones, and nNOS and interferon-gamma receptor immunoreactive structures was investigated at the lumbar level. No single retrogradely labelled spinomesencephalic, -thalamic or -hypothalamic neurone showed nNOS immunoreactivity. In the lateral spinal nucleus, however, many fluoro-gold-labelled neurones were closely apposed by both nNOS and interferon-gamma receptor immunoreactive structures, especially prominent in the hypothalamic injection cases. This study gave no evidence for nNOS immunoreactivity in spinal neurones projecting to the periaqueductal grey, thalamus or hypothalamus, but suggests that in the lateral spinal nucleus such neurones are contacted by both nNOS- and interferon-gamma receptor-containing axon terminals.