Effect of extracellular polarization on unit activity in the lateral geniculate bodies

Unit responses of the lateral geniculate bodies (LGB) to polarization of the cells through the recording microelectrode were investigated in acute experiments on cats anesthetized with Nembutal. Under the influence of anodic polarization the firing rate of the LGB cells clearly increased. Complete adaptation of the cells to the polarizing current was not observed during the time intervals investigated (5–10 min). Cathodic polarization by a current of 5–50 nA induced inhibitory effects; neurons with a single type of spontaneous activity under these circumstances generated volleys of 2–5 spikes. Off-responses were recorded in 75–85% of neurons. It is postulated that complex changes in unit activity produced by polarization may be due to the structural characteristics of the functional connections of the LGB neurons investigated. The change to grouped activity on the part of many of the neurons under the influence of cathodic polarization is evidently explained by the specific functional pattern of the synaptic system of the LGB cells.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 2, pp. 130–140, March–April, 1972.     

Effect of division of cortico — Subcortical connections on spontaneous unit activity in the lateral geniculate body and visual cortex

In acute experiments on cats the cortical projection connections of one hemisphere were divided, and the principal characteristics of spontaneous unit activity were studied in the lateral geniculate bodies (LGB) and visual cortex (area 17). After the operation the same types of spontaneous activity were found in these structures as in the intact structures. However, the number of spontaneously active cells in the structures on the side of the operation was considerably reduced. In the isolated visual cortex there was a redistribution of the relative percentage of neurons with spontaneous activity in the various layers: these cells were most numerous in layers IV–V, whereas in the normal cortex they are more numerous in layers III–IV. The mean firing rate of all types of cells was reduced in the isolated cortex. In LGB on the side of the operation a relative decrease in the number of cells with a high firing rate was observed.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 1, pp. 47–53, January–February, 1972.     

Discharge patterns of reticular neurons subjected to direct electrical polarization

The relationship between firing rate and pattern was analyzed in neurons of the mesencephalic reticular formation of curarized rats using direct polarization through the recording extracellular micropipette to simulate wide range of firing rates. 40% of initially slow irregular cells change firing pattern when accelerated and 60% remains stable. 18% of initially fast regular cells change firing pattern when retarded and 82% remains stable. Since it is generally assumed that change in firing pattern can result only from change in overall synaptic drive it is suggested that in cases firing pattern is stable the polarizing current presumably influences the value of the transmembrane potential whereas clearcut changes in firing pattern accompanying shift in mean firing rate imply the change in synaptic inflow presumably due to enhanced or decreased excitability of some part of postsynaptic membrane.     

Corticofugal control of unit responses of the cat lateral geniculate body

Acute experiments on anesthetized cats showed that blocking the projection connections of the cortex unilaterally increased the number of lateral geniculate neurons which generated long-latency phasic responses and the number of spikes in the responses of single neurons. Unit responses were monophasic more frequently in the lateral geniculate body on the side of the operation than in the same structure on the opposite side. On the basis of these results a hypothesis is developed to explain the mechanisms of monomodal descending cortical effects in microsystems of neurons of the lateral geniculate body.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 4, pp. 367–374, July–August, 1973.     

Characteristics of residual neurons during retrograde degeneration in the cat lateral geniculate body

The dynamics of structural and functional characteristics of residual neurons in the degenerating lateral geniculate body was studied in cats during the 4–12 months after division of all cortico-subcortical projection connections, including axons of relay cells of the lateral geniculate body [9]. Spontaneous and evoked activity of the residual cells, their number, and also the dimensions of the cell bodies were investigated. With lengthening of the postoperative period a decrease in the number of cells of the lateral geniculate body responding to photic stimulation and also destruction of their receptive fields were observed; 12 months after the operation the residual neurons of the lateral geniculate body lose their sensitivity to photic stimulation. Morphological investigation revealed a progressive reduction in the number of neurons in the degenerating lateral geniculate body and predominance of small neurons among them. The nature of interneuronal relations in the lateral geniculate body are discussed on the basis of the results.Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 6, pp. 575–582, November–December, 1977.     

A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus

GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting that INs may be individually tuned to optimize network operation under different input conditions.     

The development of thalamocortical connections studied by using carbocyanine dyes in the early ontogeny of rats]

We studied the differentiation of neurons and development of their connections in the occipital cortex and thalamic areas of the brain in early ontogenesis of rats: from day 11 of embryogenesis until day 19 of postnatal development. We used the method of staining of brain tissues by carbocyanine dyes after its preliminary fixation in aldehydes. Three carbocyanine dyes were used: DiI, DiO and DiA. We showed the dynamics of structural differentiation of the cortical neurons and lateral geniculate body of the thalamus and the specificity of formation of the axonal pathways between the neocortex and thalamic areas. The results obtained confirmed the hypothesis on ordered spatial-temporal growth of the cortical and thalamic fibers in early embryogenesis and revealed synchronous development of both classes of neurons of the lateral geniculate body. Retrograde and anterograde staining of the nerve cells processes by DiI and DiO showed fine morphological details of their structure. DiI provided for a good staining of the cells until day 19 of postnatal ontogenesis and DiO, until the end of embryogenesis, while DiA was not capable of diffusion in the fixed tissue.     

Dorsal thalamic connections of the ventral lateral geniculate nucleus of rats

In order to understand better the organisation of the ventral lateral geniculate nucleus of the ventral thalamus, this paper has examined the patterns of connections that this nucleus has with various nuclei of the dorsal thalamus in rats. Injections of biotinylated dextran or cholera toxin subunit B were made into the parafascicular, central lateral, posterior thalamic, medial dorsal, lateral dorsal, lateral posterior, dorsal lateral geniculate, anterior, ventral lateral, ventrobasal and medial geniculate nuclei of Sprague-Dawley rats and their brains were processed using standard tracer detection methods. Three general patterns of ventral lateral geniculate connectivity were seen. First, the parafascicular, central lateral, medial dorsal, posterior thalamic and lateral dorsal nuclei had heavy connections with the parvocellular (internal) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown previously to receive heavy inputs from many functionally diverse brainstem nuclei. Second, the visually related dorsal lateral geniculate and lateral posterior nuclei had heavy connections with the magnocellular (external) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown by previous studies to receive heavy inputs from the visual cortex and the retina. Finally, the anterior, ventral lateral, ventrobasal and medial geniculate nuclei had very sparse, if any, connections with the ventral lateral geniculate nucleus. Overall, our results strengthen the notion that one can package the ventral lateral geniculate nucleus into distinct visual (magnocellular) and non-visual (parvocellular) components.     

Origin of orientation tuning in the visual cortex.

The results of recent experiments have thrown new light on the neuronal connections underlying orientation-selective responses in the primary visual cortex of adult animals. The pattern of afferent input from the lateral geniculate nucleus to the cortex appears to be specific for orientation, while intracortical inhibitory connections appear to be non-specific in this respect. Experimental and theoretical studies have suggested that the development of cortical cell orientation tuning is an activity-dependent process.     

Effect of a polarizing current on unit activity in the respiratory center

Single unit activity in the respiratory center in the medulla was recorded in rabbits anesthetized with urethane. The neurons were polarized through the extracellular recording microelectrode by currents of different strength and polarity. In most cases a current in the positive direction (+ to the electrode tip) increased, while a negative current decreased, the firing rate. Most indices of the firing pattern of the respiratory neurons were changed by the action of the polarizing current. The coefficient of phase shift between the pneumogram and unit activity, determined by calculating the cross-correlation function between these two processes, was the most stable index. Since it takes into account the temporal and frequency characteristics of volley activity of the respiratory neurons, this coefficient can serve as a basis for their classification. The dynamics of respiratory neuronal function under subthreshold conditions was revealed by the polarization method. It was shown, in particular, that the shape of the variable component of respiratory unit activity is close to sinusoidal and differs from that suggested by the hypothesis of reciprocal interaction between two groups of neurons.Rostov State University, Rostov-on-Don. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 280–285, May–June, 1972.     

Subthalamic Nucleus High-Frequency Stimulation Restores Altered Electrophysiological Properties of Cortical Neurons in Parkinsonian Rat

Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.     

Study of interneuronal connections by the technic of luminescent demonstration of retrograde transport of primulin

A possibility to study associative and projective connections of the optic cortical fields by the method of luminescent revealing of primuline retrograde transport has been demonstrated in the experiments with cats. Initial neurons of the connective systems have been revealed in various fields of the optic cortex (fields 17, 18, 19) and in the lateral geniculate body of the thalamus. The initial cells have various luminescent intensity.     

Effect of removal of corticofugal influences on receptive fields of lateral geniculate neurons in the cat

Unilateral division of corticogeniculate connections increases the number of spikes in unit responses of the ipsilateral lateral geniculate body to receptive field stimulation and potentiates the effects of lateral inhibition. The area of the zone of complete summation of all lateral geniculate neurons recorded on the side of operation depends on contrast of the local photic stimulus. It is concluded that cortical fibers descending to the lateral geniculate body are inhibitory in nature and that the existence of receptive fields with a variable zone of spatial summation is due to intrageniculate mechanisms.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 7, No. 5, pp. 486–492, September–October, 1975.     

Mutant LGI1 inhibits seizure-induced trafficking of Kv4.2 potassium channels

Activity-dependent redistribution of ion channels mediates neuronal circuit plasticity and homeostasis, and could provide pro-epileptic or compensatory anti-epileptic responses to a seizure. Thalamocortical neurons transmit sensory information to the cerebral cortex and through reciprocal corticothalamic connections are intensely activated during a seizure. Therefore, we assessed whether a seizure alters ion channel surface expression and consequent neurophysiologic function of thalamocortical neurons. We report a seizure triggers a rapid (<2h) decrease of excitatory postsynaptic current (EPSC)-like current-induced phasic firing associated with increased transient A-type K(+) current. Seizures also rapidly redistributed the A-type K(+) channel subunit Kv4.2 to the neuronal surface implicating a molecular substrate for the increased K(+) current. Glutamate applied in vitro mimicked the effect, suggesting a direct effect of glutamatergic transmission. Importantly, leucine-rich glioma-inactivated-1 (LGI1), a secreted synaptic protein mutated to cause human partial epilepsy, regulated this seizure-induced circuit response. Human epilepsy-associated dominant-negative-truncated mutant LGI1 inhibited the seizure-induced suppression of phasic firing, increase of A-type K(+) current, and recruitment of Kv4.2 surface expression (in vivo and in vitro). The results identify a response of thalamocortical neurons to seizures involving Kv4.2 surface recruitment associated with dampened phasic firing. The results also identify impaired seizure-induced increases of A-type K(+) current as an additional defect produced by the autosomal dominant lateral temporal lobe epilepsy gene mutant that might contribute to the seizure disorder.     

Excitability of jcBNST Neurons Is Reduced in Alcohol-Dependent Animals during Protracted Alcohol Withdrawal

Alcohol dependence and withdrawal has been shown to cause neuroadaptive changes at multiple levels of the nervous system. At the neuron level, adaptations of synaptic connections have been extensively studied in a number of brain areas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrative properties of neurons. To address these problems, here, we analyze physiological properties of neurons in the bed nucleus of stria terminalis (jcBNST) in animals with a history of alcohol dependence. As a comprehensive approach, first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyze their firing responses under the action of simulated synaptic bombardment via dynamic clamp. We find that most physiological properties as measured by DC current injection are barely affected during protracted withdrawal. However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedly reduced in all 3 types of jcBNST neurons. These results support the importance of studying the effects of alcohol and drugs of abuse on the firing properties of neurons with dynamic clamp protocols designed to bring the neurons into a high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputs from the infralimbic and the insular cortices and in turn is believed to contribute to the inhibitory input to the central nucleus of the amygdala (CeA) the reduced excitability of the jcBNST during protracted withdrawal in alcohol-dependent animals will likely affect ability of the jcBNST to shape the activity and output of the CeA.     

Combined Hebbian development of geniculocortical and lateral connectivity in a model of primary visual cortex

We present a network model of visual map development in layer 4 of primary visual cortex. Our model comprises excitatory and inhibitory spiking neurons. The input to the network consists of correlated spike trains to mimick the activity of neurons in the lateral geniculate nucleus (LGN). An activity-driven Hebbian learning mechanism governs the development of both the network's lateral connectivity and feedforward projections from LGN to cortex. Plasticity of inhibitory synapses has been included into the model so as to control overall cortical activity. Even without feedforward input, Hebbian modification of the excitatory lateral connections can lead to the development of an intracortical orientation map. We have found that such an intracortical map can guide the development of feedforward connections from LGN to cortical simple cells so that the structure of the final feedforward orientation map is predetermined by the intracortical map. In a scenario in which left- and right-eye geniculocortical inputs develop sequentially one after the other, the resulting maps are therefore very similar, provided the intracortical connectivity remains unaltered. This may explain the outcome of so-called reverse lid-suture experiments, where animals are reared so that both eyes never receive input at the same time, but the orientation maps measured separately for the two eyes are nevertheless nearly identical. Received: 20 December 1999 / Accepted in revised form: 9 June 2000     

Defined cell groups in the rat suprachiasmatic nucleus have different day/night rhythms of single-unit activity in vivo

The electrical activity of the rat suprachiasmatic nucleus (SCN) was examined in anesthetized rats in vivo using single-unit electrophysiological techniques. The present data confirm the daily variation in the electrical activity of the SCN previously reported in vitro and in vivo using multiple-unit recording techniques. They further suggest that subpopulations of suprachiasmatic neurons with different neural connections have a different daily rhythm of activity. Neurons in the SCN region showed a significant rhythm of activity (p = 0.034; Kruskall-Wallis analysis of variance [KW-ANOVA]). The greatest activity occurred during the second part of the light period (ZT 10-12), and the lowest activity occurred in the early part of the light period (ZT 0-2). The subgroup of cells in the suprachiasmatic region with output projections to the arcuate nucleus (ARC) and/or supraoptic nucleus (SON) regions also showed a significant rhythm (p = 0.001; K-W ANOVA). Their activity appeared to show two peaks near the light-dark (ZT 10-12) and dark-light (ZT 22-24) transition periods with the lowest activity at ZT 16-18. This rhythm was significantly different (p = 0.016) from that of neurons without an output projection to the ARC and/or SON. Retinorecipient suprachiasmatic neurons appeared to have a less robust daily rhythm in their activity. The change in the firing behavior of the cells was not reflected simply by changes in mean firing rate. Examination of the coefficient of variation of the interspike interval distribution of cells at different times of day revealed changes in the firing pattern of cells in the SCN region that did not have output projections (p = 0.032; K-W ANOVA). The present results thus suggest that the SCN is composed of a heterogeneous population of neurons and that different rhythms of activity are expressed by neurons with different neural connections. There were changes in both firing pattern and firing rate.     

Hypothalamic control of visual cortical unit activity in rabbits

During the action of an extracellular polarizing current on neurons of the rabbit visual cortex electrical stimulation was applied to various hypothalamic nuclei (preoptic region, anterior hypothalamic region, lateral hypothalamus, mammillary bodies, and posterior hypothalamic nucleus). Hypothalamic stimulation was found to reduce the mean discharge frequency of most visual cortical neurons tested under conditions of anodal polarization, when the initial level of activity is considerably increased, than to a decrease in activity under conditions of cathodal polarization, when the initial level of activity is considerably reduced. The same tendency toward restoration of the initial (spontaneous) level of unit activity after hypothalamic stimulation was discovered when this level was shifted as a result of stimulation by regular flashes. The greatest effect was observed during stimulation of the preoptic region of the hypothalamus. Stimulation of the posterior hypothalamic nucleus was least effective in this respect.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 469–476, September–October, 1977.     

大鼠上丘到外膝体P－物质投射的机能

已知大鼠外膝体内有中脑上丘来的含Ｐ－物质的神经末梢,其机能不明。在离休的大鼠外膝体脑片上用单电极电压箝位的方法研究了Ｐ－物质对外膝体神经元电压依赖性离子通道的作用。结果表明,Ｐ－物质可以使静息膜去极化,并降低膜电导。这提示Ｐ－物质抑制了线性钾漏电流。此外,Ｐ－物质还抑制去极化激活的慢失活的钾电流、低阈值钙电流和超极化激活的内向整流（Ｈ或Ｑ）电流。Ｐ－物质还可能抑制早钾（Ａ）电流。因此,Ｐ－物质在外膝体视觉信号传递中的作用是使外膝体神经元从爆发反应方式或振荡状态转化为中继反应方式,易化突触传递,使视网膜的视觉信号忠实地传递到大脑皮层。     

Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus

Biphasic neural response properties, where the optimal stimulus for driving a neural response changes from one stimulus pattern to the opposite stimulus pattern over short periods of time, have been described in several visual areas, including lateral geniculate nucleus (LGN), primary visual cortex (V1), and middle temporal area (MT). We describe a hierarchical model of predictive coding and simulations that capture these temporal variations in neuronal response properties. We focus on the LGN-V1 circuit and find that after training on natural images the model exhibits the brain's LGN-V1 connectivity structure, in which the structure of V1 receptive fields is linked to the spatial alignment and properties of center-surround cells in the LGN. In addition, the spatio-temporal response profile of LGN model neurons is biphasic in structure, resembling the biphasic response structure of neurons in cat LGN. Moreover, the model displays a specific pattern of influence of feedback, where LGN receptive fields that are aligned over a simple cell receptive field zone of the same polarity decrease their responses while neurons of opposite polarity increase their responses with feedback. This phase-reversed pattern of influence was recently observed in neurophysiology. These results corroborate the idea that predictive feedback is a general coding strategy in the brain.