Characteristics of synaptic connections between rodent primary somatosensory and motor cortices

The reciprocal connections between primary motor (M1) and primary somatosensory cortices (S1) are hypothesized to play a crucial role in the ability to update motor plans in response to changes in the sensory periphery. These interactions provide M1 with information about the sensory environment that in turn signals S1 with anticipatory knowledge of ongoing motor plans. In order to examine the synaptic basis of sensorimotor feedforward (S1-M1) and feedback (M1-S1) connections directly, we utilized whole-cell recordings in slices that preserve these reciprocal sensorimotor connections. Our findings indicate that these regions are connected via direct monosynaptic connections in both directions. Larger magnitude responses were observed in the feedforward direction (S1-M1), while the feedback (M1-S1) responses occurred at shorter latencies. The morphology as well as the intrinsic firing properties of the neurons in these pathways indicates that both excitatory and inhibitory neurons are targeted. Differences in synaptic physiology suggest that there exist specializations within the sensorimotor pathway that may allow for the rapid updating of sensory-motor processing within the cortex in response to changes in the sensory periphery.     

Characteristics of synaptic connections between rodent primary somatosensory and motor cortices

The reciprocal connections between primary motor (M1) and primary somatosensory cortices (S1) are hypothesized to play a crucial role in the ability to update motor plans in response to changes in the sensory periphery. These interactions provide M1 with information about the sensory environment that in turn signals S1 with anticipatory knowledge of ongoing motor plans. In order to examine the synaptic basis of sensorimotor feedforward (S1–M1) and feedback (M1–S1) connections directly, we utilized whole-cell recordings in slices that preserve these reciprocal sensorimotor connections. Our findings indicate that these regions are connected via direct monosynaptic connections in both directions. Larger magnitude responses were observed in the feedforward direction (S1–M1), while the feedback (M1–S1) responses occurred at shorter latencies. The morphology as well as the intrinsic firing properties of the neurons in these pathways indicates that both excitatory and inhibitory neurons are targeted. Differences in synaptic physiology suggest that there exist specializations within the sensorimotor pathway that may allow for the rapid updating of sensory–motor processing within the cortex in response to changes in the sensory periphery.     

Arrangement and afferent connections of the neurons in the visual cortex differing in the size of the receptive fields

In the area 17 of the cerebral cortex of guinea pigs cells with small and medial receptive fields (RF) are concentrated at the sites of separate groupings of neurons excited by flashes of diffusion light. There are also cells with large RF here. At such sites of the cortex when specific afferents are electrically stimulated many cells exhibit monosynaptic activation irrespective of their RF size. The main part of the neurons with large RF is situated in the areas of the cortex between the excited grouping and monosynaptical excitation is not inherent in such neurons. Most cells of these areas are not excited by specific afferents.     

Long-range neuronal circuits underlying the interaction between sensory and motor cortex

In the rodent vibrissal system, active sensation and sensorimotor integration are mediated in part by connections between barrel cortex and vibrissal motor cortex. Little is known about how these structures interact at the level of neurons. We used Channelrhodopsin-2 (ChR2) expression, combined with anterograde and retrograde labeling, to map connections between barrel cortex and pyramidal neurons in mouse motor cortex. Barrel cortex axons preferentially targeted upper layer (L2/3, L5A) neurons in motor cortex; input to neurons projecting back to barrel cortex was particularly strong. Barrel cortex input to deeper layers (L5B, L6) of motor cortex, including neurons projecting to the brainstem, was weak, despite pronounced geometric overlap of dendrites with axons from barrel cortex. Neurons in different layers received barrel cortex input within stereotyped dendritic domains. The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning.     

Intercentral relations of the electrical processes of the rabbit brain with a polarization dominant

The dynamics of changes in intercentral relations of electrical activity of the sensorimotor and premotor zones of both hemispheres and the ventroposterolateral (VPL) nucleus of the left and right thalamus at formation of motor dominant under the action of the DC anode in the rabbit sensorimotor cortex was studied by the method of spectral-correlation analysis. It is shown that in the much less than dominant much greater than motor analyzer (the sensorimotor cortex and VPL) highly coherent connections of electrical processes are formed in the delta-range with conjugated lowering of biopotential connections between the structures of the motor analyzer of the much less than nondominant much greater than part of the brain. At the same time differently directed connections of electrical processes are formed between the structures of the motor analyzer, and between the premotor cortex and focus area. Thus, during formation of the much less than polarization much greater than dominant, a new structure of the intercentral relations of electrical processes is established not only in the much less than dominant much greater than but also in the other half of the brain.     

Callosal neurons: monosynaptic connection between them and their descending projections

Antidromic and monosynaptic unit responses to the stimulation of the corpus callosum and the symmetrical cortical area as well as antidromic responses to pyramidal tract and thalamic nuclei stimulation were recorded in the sensorimotor cortex of unanaesthetized rabbits. Out of 182 callosal neurones 13 exhibited transcallosal monosynaptic responses. 8 out of 56 callosal units responded antidromically to pyramidal tract or thalamic stimulation. Thus callosal neurones may be monosynaptically excited by callosal units via the corpus callosum and by the pyramidal tract units. It was also found that a pyramidal tract neurone may send a collateral through the corpus callosum and at the same time have a transcallosal monosynaptic input. The role of monosynaptic transcallosal excitation of callosal neurones is discussed.     

The heterogeneity of the excitatory synaptic inputs in the spinal motor neurons of the frog Rana ridibunda

The synaptic responses induced in motoneurones by the stimulations of the dorsal root (DR), single afferent fibres and reticular formation (RF) were intracellularly recorded in the isolated frog spinal cord. It was shown that argiopine (the selective blocker of glutamate receptors of non-NMDA type) in concentrations ranging from 3.10(-7) to 1.10(-5) M effectively suppressed the di- and polysynaptic, but not the monosynaptic components of EPSP's induced by DR stimulation. The initial reaction to argiopine consisted of the increase of this monosynaptic component of EPSP. In the same concentrations range, argiopine reduced both mono- and polysynaptic EPSP, evoked by RF stimulation. 2-amino-phosphonovaleric acid (1.10(-4) M) did not affect, whereas the kinurenate (1--2.10(-3) M) completely blocked the amplitude of all kinds of synaptic responses. The various effects of argiopine on the responses induced by microstimulation of presynaptic nerve terminals were observed. The data obtained speak in favour of heterogeneity of monosynaptic excitatory inputs in the motoneurones of frog spinal cord. Being the glutamatergic by nature, the inputs differ in the properties of postsynaptic receptors. All of these receptors concerning to non NMDA-type can be divided to argiopine-sensitive and argiopine-resistant. The first seem to be involved in the monosynaptic connections of RF and the second--in those of primary afferents with motoneurones.     

Responsiveness of Reorganized Primary Somatosensory (SI) Cortex after Local Inactivation of Normal SI Cortex in Chronic Spinal Cats

The cortical map of adult cats that sustained spinal cord transection at T₁₂ when they were 2 weeks old is characterized by a clear duplication of the representation of the forelimb, rostral trunk, and neck. The novel representation is located in the cortical region that is, in nonoperated animals, normally devoted to the hindlimb representation. We have investigated the possibility that the reactivation of the deprived hindlimb cortex may be mediated by corticocortical projections from normal to reorganized cortex. The primary somatosensory (SI) cortex was initially mapped to determine the boundaries of the normal and reorganized cortical representations. Somatotopically corresponding regions in both normal and reorganized cortex representing the trunk, the web space, or the shoulder were more precisely mapped. Inactivation of normal cortex was achieved by the nanoinjection of a solution of lidocaine hydrochloride stained with Chicago sky blue. Two major findings are described. First, inactivation of a circumscribed region of normal cortex representing a given receptive field (RF) failed to reduce or inhibit the responsiveness of a somatotopically corresponding RF represented in reorganized cortex. Therefore, it is unlikely that intracortical connections between normal and reorganized cortex could account for the reorganizational processes observed in cats that sustained spinal cord transection at 2 weeks of age. Second, the chemical blockade of normal cortex provoked an increase of the responsiveness and of the size of the peripheral RFs represented in reorganized cortex. This finding suggests that there are corticocortical connections (possibly topographically organized) between normal and reorganized cortex, and that these connections are inhibitory.     

Responsiveness of reorganized primary somatosensory (SI) cortex after local inactivation of normal SI cortex in chronic spinal cats.

The cortical map of adult cats that sustained spinal cord transection at T12 when they were 2 weeks old is characterized by a clear duplication of the representation of the forelimb, rostral trunk, and neck. The novel representation is located in the cortical region that is, in nonoperated animals, normally devoted to the hindlimb representation. We have investigated the possibility that the reactivation of the deprived hindlimb cortex may be mediated by corticocortical projections from normal to reorganized cortex. The primary somatosensory (SI) cortex was initially mapped to determine the boundaries of the normal and reorganized cortical representations. Somatotopically corresponding regions in both normal and reorganized cortex representing the trunk, the web space, or the shoulder were more precisely mapped. Inactivation of normal cortex was achieved by the nanoinjection of a solution of lidocaine hydrochloride stained with Chicago sky blue. Two major findings are described. First, inactivation of a circumscribed region of normal cortex representing a given receptive field (RF) failed to reduce or inhibit the responsiveness of a somatotopically corresponding RF represented in reorganized cortex. Therefore, it is unlikely that intracortical connections between normal and reorganized cortex could account for the reorganizational processes observed in cats that sustained spinal cord transection at 2 weeks of age. Second, the chemical blockade of normal cortex provoked an increase of the responsiveness and of the size of the peripheral RFs represented in reorganized cortex. This finding suggests that there are corticocortical connections (possibly topographically organized) between normal and reorganized cortex, and that these connections are inhibitory.     

Studies of functional connectivity in the developing and mature visual cortex

We have investigated several aspects of cortical organization in adult cats and in young kittens. First, we determined receptive field (RF) maps of correlated discharge between pairs of cortical cells. Unique bicellular RFs appear to convey high resolution information. Second, we studied the dynamics of neural interaction between pairs of cells. Using cross-correlation analysis, we studied monosynaptic and polysynaptic interactions in both kittens and cats. A somewhat surprising finding is that there were no cases of monosynaptic excitation from simple to complex cells as would be predicted by a simple hierarchical processing theory. Third, we studied length and side tuning characteristics of cortical cells and worked out the relationships between them. Fourth, we carried out an investigation of binocular processing in which we compared monocular and binocular sensitivity of cortical cells with respect to contrast. Our results are comparable to those found in psychophysical work. Fifth, we examined how stereoscopic depth information is encoded by simple cells in the visual cortex. We show that structural differences in RFs of left and right eyes may be expressed in terms of phase. Phase-based encoding appears to be a very plausible alternative to the standard position-based notion. Sixth, we attempted to induce plastic changes in connections between cell pairs by long-term activation (up to 2 h) in kittens and cats. Although connection strength between some cell pairs was increased during long-term activation, there was no consistent pattern of this effect. Seventh, we attempted to study the functional basis of reported claims of RF expansion following use of an artificial scotoma. However, we found no receptive field size change from this procedure. For some cells, there is an apparent change of gain in the form of base (spontaneous) rates and absolute response levels. Finally, we have examined RF dynamics in the central visual pathways. The standard treatment of RFs is to consider only spatial aspects. But the RF is inherently both temporal and spatial in nature and we have examined the dynamics of spatiotemporal organization of RFs in central visual pathways.     

Raised excitability produced in cortical neurons by reinforced stimulation of the lateral hypothalamus

Response was recorded in the pyramidal tract (PT) under three experimental situations modelling the shaping of conditioned reflex (CR) during experiments on unrestrained but unanesthetized rabbits. The first paradigm consisted of direct stimulation of two points on the sensorimotor cortex, the second of the same stimuli combine with electrical stimulation (used as additional reinforcement) of the lateral hypothalamus (LH), and the third of LH stimulation in response to a rise occurring in PT response to above control level (modelling instrumental CR). An overall increase in the monosynaptic wave indicative of altered efficacy of synaptic connections was most commonly observed under all these conditions. Increase in the component directly reflecting pyramidal neuronal excitation appeared significantly more pronounced in the second and third than in the first experimental paradigm. The data obtained would point to reinforced efficacy of excitatory synaptic connections as the principal mechanism of CR, while the changed quality of electrical excitability at the membrane of cortical neurons reflects mechanisms underlying the contribution of reinforcement triggered by LH activation in cortical reordering of the motivational/emotional component of reinforcement.Higher Nervous Activity and Neurophysiology Research Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 6, pp. 805–811, November–December, 1989.     

Corticofugal postsynaptic influences on red nucleus neurons

The responses of red nucleus neurons to stimulation of the sensorimotor cortex was studied on nembutal-anesthetized cats. Most of the rubrospinal neurons were identified according to their antidromic activation. Stimulation of the sensorimotor cortex was shown to evoke in the red nucleus neurons monosynaptic excitatory potentials with a latency of 1.85 msec, polysynaptic excitatory potentials (EPSP), and inhibitory postsynaptic potentials (IPSP) with a latency of 9–24 msec. The EPSP often produced spikes. The probability of generation of spreading excitation is greater with motor cortex stimulation. The monosynaptic EPSP are assumed to arise under the influence of the impulses arriving over the corticorubral neurons as a result of excitation of axodendritic synapses. The radial type of branching of red nucleus neurons facilitates the transition from electrotonically spreading local depolarization to an action potential triggered by the initial axonal segment. Polysynaptic EPSP and IPSP seem to be a result of activation of fast pyramidal neurons whose axon collaterals are connected via interneurons with the soma of the red nucleus neurons.L. A. Orbeli Institute of Physiology of the Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 43–51, January–February, 1971.     

Activation of cat pontine nuclei neurons produced by cortico- and cerebellofugal impulses

Extracellular recording techniques were used on cats anesthetized with Nembutal to illustrate antidromic activation of pontine neurons produced by stimulating the medial and occasionally the superior cerebellar peduncle, the cerebellar central nuclei, pyramidal tract, and sensorimotor region of the cortex. Of the pontine nucleus projection, that extending to the lateral cerebellar nucleus was the most clearly defined. Stimulation of the pyramidal tract, central cerebellar nuclei and the superior cerebellar peduncle was found to produce monosynaptic excitation of pontine neurons. The significance and special features of the connections identified are discussed in connection with cortico-pontocerebellar system function.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Amenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 38–48, January–February, 1988.     

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.     

Post-tetanic modification of the efficacy of excitatory transmission in neuronal networks with interhemispheric connections

The modifiable reciprocal transcallosal monosynaptic excitatory connections were for the first time detected in vivo experiments in rat motor cortex using multiunit recording and crosscorrelation analysis, It was shown that high-frequency microstimulation (MCS) of a small group of cortical cells of one hemisphere produces long-term changes in the efficacy of transcallosal excitatory connections, and also ipsilateral connections in both hemispheres. The posttetanic changes appear as long-term potentiation (LTP) and long-term depression (LTD). The bursting neurons were found to have more favorable conditions for the induction of LTP of most converging inputs (in contrast to cells with other discharge patterns). Both LTP and LTD could be simultaneously induced in synapses formed by axon collaterals of a callosal cell on several neurons. LTP and LTD could be simultaneously obtained at diverse synapses of the same cell. The number of spontaneously active callosal neurons as well as the number and efficacy of transcallosal connections increased after the MCS, whereas the number and efficacy of ipsilateral connections decreased. Basing on these data we assume that the ipsilateral inhibition is more effective than the transcallosal inhibition. MCS results in the modification of the pattern of initially existing connections between numerous neurons of an ensemble including cells of both hemispheres.     

Comparative analysis of the interactions between spontaneous active neurons of the sensomotor cortex of kittens and adult cats

The character of functional interneuronal relations in the sensorimotor cortex during spontaneous neural activity in kitten and adult cats immobilized with d-tubocurarine, was studied by the method of cross-correlations of two impulse series. The data obtained by computation revealed specific age-related interneuronal connections in investigated groups of animals. In kitten aged up to 10 days, the highest percentage of the functional connections was observed which were established mainly due to the influence of a common source. In other groups of animals (kittens of 20, 30 days of postnatal life, adult cats) the common source did not play a significant role in the formation of interneuronal connections. The results showed that inhibitory connections between neurones-are established to the end of the first month of the postnatal life.     

Environmental enrichment modulates cortico-cortical interactions in the mouse

Environmental enrichment (EE) is an experimental protocol based on a complex sensorimotor stimulation that dramatically affects brain development. While it is widely believed that the effects of EE result from the unique combination of different sensory and motor stimuli, it is not known whether and how cortico-cortical interactions are shaped by EE. Since the primary visual cortex (V1) is one of the best characterized targets of EE, we looked for direct cortico-cortical projections impinging on V1, and we identified a direct monosynaptic connection between motor cortex and V1 in the mouse brain. To measure the interactions between these areas under standard and EE rearing conditions, we used simultaneous recordings of local field potentials (LFPs) in awake, freely moving animals. LFP signals were analyzed by using different methods of linear and nonlinear analysis of time series (cross-correlation, mutual information, phase synchronization). We found that EE decreases the level of coupling between the electrical activities of the two cortical regions with respect to the control group. From a functional point of view, our results indicate, for the first time, that an enhanced sensorimotor experience impacts on the brain by affecting the functional crosstalk between different cortical areas.     

Electrophysiological and histological study of synaptic connections between lateral geniculate transplant and host visual cortex

The lateral geniculate nucleus (LGN) of fetal Wistar rats was transplanted to the visual cortex (VC) of 33 neonatal Wistar rats. Histological examination showed transplanted cells in all the host brains. Intensively labeled cells were demonstrated in the transplant by labeling with true blue. Electrophysiological studies with brain slice preparations demonstrated that the transplanted LGN sent axons and made excitatory monosynaptic connections mainly in layer IV of the VC area 17. Corticogeniculate projections were also demonstrated in the transplanted LGN.     

Afferent and efferent connections of cortical transplants implanted into the damaged sensorimotor area of the cerebral cortex of mature rats

Afferent and efferent connections of the transplant, implanted in the previously damaged sensorimotor area of the mature rat cerebral cortex have been studied by means of axonal transport of horseradish peroxidase. For 5 months after transplantation neural axons of the transplant are capable to reach the caudo-putamen and thalamic structures, while connections with the spinal cord are absent. The afferent connections of the transplant are minimal and belong only to the neighbouring areas of the cortex and the caudo-putamen of the recipient brain. Presence of efferent projections to the striate and thalamic structures demonstrates specificity of the projections formed; this can be a morphological base for restoration of the functions lost after the damage of the sensorimotor area of the cortex in mature animals.     

Development of a MR-visible compound for tracing neuroanatomical connections in vivo

Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in?vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (S1) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.7T and?7T. The transported GdDOTA-CTB was visible for at least 1?month post-injection, clearing within 2?months. Control injections of non-conjugated GdDOTA into S1 were not transported and cleared within 1-2?days. Control injections of Gd-Albumin were not transported either, clearing within 7?days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The?GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.