The effect of electrical stimulation of the locus coeruleus on the neuronal activity of the parietal associative cortex

In experiments performed on cats operated under ketamine anaesthesia and subsequently immobilized by myorelaxin it was demonstrated that locus coeruleus (LC) being stimulated by a train of pulses can exert influence on 79% of parietal cortex neurons. Inhibition of the background activity for 300-700 ms or a decrease in its frequency by 16-32% were observed in them after the LC stimulation. During intracellular recording neurons with background activity and "silent" neurons responded to LC stimulation by hyperpolarization (5-7 mV) lasting for 120-500 ms with latency of 30-90 ms. The duration of the inhibitory pause in background activity caused by transcallosal stimulation increased by 50-200 ms due to conditioning stimulation of LC. The duration of IPSPs evoked by transcallosal stimulation also increased by 50-100 ms under the influence of LC stimulation. It is concluded that the influence of LC stimulation on the activity of the parietal cortex neurons can be exerted either directly as inhibition of background activity and hyperpolarization or as modulation of effects of other neurotransmitters.     

Inhibitory influences of reticulospinal fibers of the lateral funiculus on neurons of the reflex arc of the thoracic region of the spinal cord

Experiments on anesthetized cats with partial lesions of the spinal cord show that reticulospinal pathways in the ventral part of the lateral funiculus take part in the polysynaptic reflex inhibition caused by stimulation of ipsi- and contralateral reticular formation. The reticulofugal volley in the ventrolateral funiculus produced relatively short (up to 7 ms) inhibitory PSP in some motoneurons of the internal intercostal nerve and at the same time long-lasting depression of EPSPs evoked by high-threshold segmentary afferents. This volley also caused inhibitory PSP in segmental interneurons (in 14 out of 91, i.e. 15.5%). The IPSPs lasted no longer than 100 ms, while the segmentary excitatory responses of 21 out of 43 interneurons were depressed for 120-500 ms. The described inhibitory action of the lateral reticulospinal system on segmentary reflex pathways is suggested to be caused by several synaptic mechanisms which do not necessarily include hyperpolarization of spinal neurons. Possible mechanisms of such inhibition are discussed.     

Weaker synaptic inhibition in CA1 region of ventral compared to dorsal rat hippocampal slices

Extracellular and intracellular recordings were made from slices taken from the dorsal (DH) and ventral (VH) part of rat hippocampus. Using paired-pulse stimulation of Schaffer collaterals, at different interpulse intervals (IPIs), and records of the population spike (PS) we found that the strength and duration of paired-pulse inhibition was much weaker in VH compared to DH slices: at the IPI of 10 ms the decrease of PS in VH (40%) was significantly smaller compared to that in DH slices (76%), while at 20 ms the decrease of PS in DH slices (60%) corresponded to facilitation in VH slices. Moreover, the amplitude and duration of intracellularly recorded fast inhibitory postsynaptic potentials (fast-IPSPs) were found significantly smaller in VH (5.2+/-0.6 mV, 54.8+/-5.8 ms) than in DH (11.2+/-1.1 mV, 105+/-10 ms) neurons. The smaller and shorter fast-IPSP recorded in VH neurons may at least in part explain the results in paired-pulse inhibition. The demonstrated weaker inhibition may underlie the higher propensity of the ventral hippocampus for epileptiform activity.     

Changes in mechanoreceptive field properties of trigeminal somatosensory brainstem neurons induced by stimulation of nucleus raphe magnus in cats

Experiments were carried out on adult anesthetized cats in which the effects of nucleus raphe magnus (NRM) conditioning stimulation (20 ms) were tested on the responses evoked by orofacial stimuli in single brainstem neurons of trigeminal (V) subnucleus oralis. The NRM stimulation induced inhibition of the responses of 57 of 77 low-threshold mechanoreceptive (LTM) neurons and the one wide-dynamic range (WDR) neuron tested. The duration of the neuronal inhibition ranged from 300-600 ms and the mean threshold for inhibition ranged from 47.8 +/- 4.8 to 102.7 +/- 15 microA depending on the orofacial stimulation site (skin or tooth pulp) and form (mechanical or electrical) of cutaneous stimuli used to evoke neuronal responses. In 20 LTM neurons showing NRM-induced inhibition that were specifically examined for the effects of NRM stimulation on the mechanoreceptive field, one population (n = 11) showed shrinkage (mean 55 +/- 4.4% from control area) of the mechanoreceptive field while the remaining neurons (n = 9) showed no change in mechanoreceptive field size during NRM stimulation. The former group of neurons were also distinguished from the latter neurons by their significantly larger mechanoreceptive field and the activation of the majority of them by electrical stimuli applied outside their mechanoreceptive field. The responses of these neurons evoked by low-threshold inputs from the edge of the mechanoreceptive field were more sensitive to NRM conditioning stimulation than responses evoked from the mechanoreceptive field center, as judged by threshold, magnitude and duration of the NRM-induced inhibition. These findings underscore the sensitivity of LTM neurons to NRM influences. They also reveal a particular population of oralis neurons which have a differential sensitivity of low-threshold inputs evoked from the edge compared to the center of the mechanoreceptive field.     

Feedback inhibition in microsegments of the visual cortex]

Interaction between 3-4 neighbouring neurons in the visual cortex of awakening cats was examined using a cross-correlation analysis. In some microsystems neurons revealed a tendency towards synchronized activity indicating a shared excitatory input. In other microsystems asymmetrical interaction was observed: neurons with larger spike amplitudes exhibited excitatory effect on neurons with smaller spike amplitudes (latent period about 5 ms) and neurons with small spike amplitudes inhibited neurons with large spike amplitudes (latent period 1-8 ms, duration of inhibition 30-200 ms). Suggestions were made about the existence of recurrent inhibition and inhibitory interneurons in microsystems of the visual cortex.     

Intracellular responses of the rat anteroventral cochlear nucleus to intracochlear electrical stimulation

The anteroventral cochlear nucleus (AVCN) is the first central processing site for acoustic information. The influence and extent of convergent auditory nerve input to AVCN neurons was investigated using brief (<0.2 ms) intracochlear electrical activation of spiral ganglion cells. In 40 neurons recorded in vivo, the major intracellular response to stimulation was an excitatory postsynaptic potential (EPSP) with short latency (∼1 ms) and fast rise time (<1 ms). Graduated EPSP amplitude increases were also seen with increasing stimulation strength resulting in spike generation. Hyperpolarization followed excitation in most neurons, its extent distinguished three response types: Type I showed no hyperpolarization; Type II and Type III displayed short (<10 ms) and long (>19 ms) duration hyperpolarization, respectively. Hyperpolarization was attributed to an inhibitory postsynaptic potential (IPSP) in addition to spike after hyperpolarization. Neurobiotin filling identified Type I and II neurons as stellate and Type III as bushy cells. These results suggests that AVCN neurons receive direct, possibly convergent, excitatory input from auditory nerves emanating from spiral ganglion cells with hyperpolarization resulting from polysynaptic inhibitory input.     

The inhibitory input from the substantia nigra to the mediodorsal nucleus neurons projecting to the prefrontal cortex in the cat

The effects of stimulation of the substantia nigra pars reticulata (SNr) on the neurons of the mediodorsal nucleus (MD) projecting to the prefrontal cortex (PF) were studied in cats. The MD neurons projecting to the ventral part of the PF tended to be located in the ventral part of the MD, while those projecting to the dorsal part of the PF in the dorsal part. Spontaneous discharges of 30/57 tested MD neurons were suppressed by SNr stimulation at a latency ranging from 2 to 15 ms. The latency of the suppression corresponded well to that of antidromic responses of SNr neurons elicited by MD stimulation (from 1.4 to 14.0 ms). Intracellular recordings in a few MD neurons showed IPSP by SNr stimulation. The SNr is considered to exert an inhibitory effect on the MD neurons projecting to the PF.     

Reactions of neurons in the primary and secondary somatosensory zones of the cortex to stimulation of the ventral posterior nucleus of the thalamus]

Neuronal responses in the first and second somatosensory cortex (SI and SII) to stimulation of the ventroposterior nucleus of the thalamus (VP) were studied in experiments on cats immobilized with d-tubocurarine. 12.0% responding neurons in SI and 9.5% in SII were activated antidromically by VP stimulation. In the majority of antidromic responses the latencies did not exceed 1.0 ms. The minimal latency of orthodromic spikes was 1.5 ms in SI and 1.7 ms in SII. In SI the number of neurons whose orthodromic spike latencies did not exceed 3.0 ms was larger than neurons activated with latencies of 3.1-4.5 ms. In SII an inverse quantitative relationship between those two neuronal groups was observed. In SII a significantly larger number of neurons was excited with latencies of EPSPs ranged between 1.1-9.0 ms in SI and between 1.4-6.6 ms in SII and the latencies of IPSPs between 1.5-6.8 ms in SI and 2.2-9.4 ms in SII. The importance of different pathways for excitatory and inhibitory VP influences to neurons of SI and SII is discussed.     

Different cardiovascular neuron groups in the ventral reticular formation of the rostral medulla in rabbits: single neurone studies

To examine whether the cardiovascular neurons of the ventral medulla consist of functionally different kinds of neurons, single neuronal activity of the ventral medulla, activity of the renal sympathetic nerves (RSNA), blood flow of the ear (EarBF) and arterial pressure (AP) were recorded in urethane-anesthetized, vagotomized and immobilized rabbits during electrical stimulation of the aortic nerve (AN, baroreceptor afferent fibers) and electrical stimulation of the dorsomedial hypothalamus (DMH) that reduced EarBF but less affected on AP and RSNA. The dorsolateral funiculus of the second cervical cord was stimulated to evoke antidromic spikes of medullary neurons. Two kinds of reticulo-spinal neurons were identified. Activities of one kind of neurons were facilitated by stimulation of DMH (latency 48.6+/-27.6 ms, n=11) but they did not respond to stimulation of the AN. Therefore, it was presumed that these neurons controlled vasomotion of the ear through the vasoconstrictor neurons in the spinal cord but did not participate in regulation of systemic AP. Activities of the other neurons were inhibited by stimulation of the AN (latency 47.8+/-8 4 ms, n=16) but they did not respond to the DMH stimulation. These neurons were identical to those reported previously as the RVLM neurons, and they contributed to regulate systemic AP but might not participate in control of cutaneous vascular movement. The former neurons were located medially to the latter in the reticular formation of the rostral ventral medulla. These results provided evidence at the single neuronal level that the cardiovascular neurons in the ventral medulla were consisted of functionally different sympatho-excitatory neurons and they were located at the different sites in the rostral ventral medulla.     

The termination in the mesencephalon of fibres from the lateral cervical nucleus. An anatomical study in the cat

The aim of the present study was to determine the identity of the neurotransmitter released by the pathway from the subthalamic nucleus to the entopeduncular nucleus in the rat, using extracellular stimulating and recording techniques and microiontophoresis. In order to avoid stimulation of passing fibers at the level of the subthalamic nucleus, (collaterals to the entopeduncular nucleus of the caudato-nigral pathway, or direct projections to the entopeduncular nucleus from the substantia nigra or nucleus tegmenti pedunculopontinus), the experiments were performed in rats bearing chronic ipsilateral lesions in order to make these pathways degenerate. Under such conditions, subthalamic nucleus stimulation suppressed the spontaneous firing of all the entopeduncular nucleus cells studied (n = 40) for 15-25 ms (mean duration +/- S.E.M.:21.88 +/- 1.57 ms). Entopeduncular nucleus cells were identified by antidromic activation from the ventral anterior thalamic nucleus (40%) or lateral habenula nucleus (68%). Low doses of iontophoretically applied GABA (60 cells) or glycine (15 cells) were inhibitory upon entopeduncular cells, while acetylcholine or carbamylcholine were poorly excitatory (18 cells), or had no effect (28 cells). The subthalamic nucleus-evoked inhibition of entopeduncular neurons was reversed by microiontophoretically applied bicuculline or picrotoxin, at doses which blocked the GABA-induced response, but not that produced by glycine or acetylcholine. With similar experiments, strychnine and atropine were ineffective. This excludes a possible role of glycine or acetylcholine in the subthalamic-evoked inhibitory response of entopeduncular cells. The present study strongly suggest that GABA is a neurotransmitter in the inhibitory subthalamo-entopeduncular pathway.     

Reactions of the neurons of the reticular and ventral anterior nuclei of the optic thalamus to afferent stimulation of different modalities]

Responses of 146 reticular (R) and 98 ventral anterior (VA) thalamic neurons to electrical stimulation of pads, to light flashes and sound clicks were studied in cats immobilized with d-tubocurarine or myorelaxine. The contralateral forepaw was the most effective receptive field: 24.9% of R and 31.3% of VA investigated neurons responded to its stimulation. Only 4.4% of R and 2.4% of VA neurons responded to the click. Almost all responding neurons reacted to different kind of the applied stimulation by phasic or tonic excitation. Inhibition of background activity was observed after the pads stimulation only in 2.6-4.3% of R and in 1.7%-2.1% of VA neurons. The latency of phasic responses in most neurons ranged: to electrical stimulation of the contralateral forepaw from 6 to 64 ms, to the contralateral hindpaw -- from 11 to 43 ms, to light -- 10-60 ms, and to the click -- 8-60 ms. 75.1-95.6% of R and 68.7-97.6% of VA neurons did not respond at all to different kinds of peripheral stimulation. Of a sample of cells tested to all inputs 25% of R and 47% of VA neurons responded to stimulation of more than one paw; 16% of R and 22% of VA neurons revealed convergence of volleys of different modality. The functional role of this convergence consists in inhibition (more seldom facilitation) of the neuronal response to a testing signal following 40-70 ms after a conditioning one.     

Cardiovascular afferent and fastigial nucleus inputs to paramedian reticulospinal neurons

In chloralose anesthetized, paralyzed and artificially ventilated cats, the region of the paramedian reticular nucleus (PRN) was systematically explored for single units antidromically activated by electrical stimulation of histologically verified sites in the intermediate gray region of the upper thoracic cord (T2). These antidromically identified units were then tested for their orthodromic responses to electrical stimulation of ipsilateral carotid sinus nerve (CSN) and of pressor sites in the contralateral fastigial nucleus (FN). Sixty-two histologically verified single units, located predominantly in the caudal half of the ventral PRN, were antidromically activated with latencies corresponding to a mean conduction velocity of 36.4 +/- 2.1 m/s. Of these units 25 (40%) were excited orthodromically by stimulation of the CSN and/or FN: 5 to stimulation of the CSN only (mean latency, 18.3 +/- 9.9 ms), 6 to stimulation of the FN only (mean latency, 7 +/- 1.7 ms), and 14 to stimulation of both the CSN and FN (mean latencies, 12.3 +/- 2.9 ms and 8.4 +/- 1 ms, respectively). These data provide electrophysiological evidence for the existence of PRN reticulo-spinal neurons that integrate and relay cardiovascular afferent information from the CSN and FN to spinal autonomic neurons.     

Inhibition and synchronisation of tremor induced by a muscle twitch.

The effects of a muscle twitch on the tremor of the extensor indicis muscle and of the tibial anterior muscle have been recorded in 14 patients with essential tremor and in 10 patients with Parkinson's disease. The muscle twitch evoked by the electrical stimulation of the motor nerve inhibits the tremor and synchronises it. The mean duration of the inhibition is 92.1 +/- 6.8 ms for essential tremor and 183.0 +/- 16.8 ms for Parkinsonian tremor. This inhibitory phase lasts longer when the muscle twitch is induced during the second half of the Parkinsonian tremor cycle. The effects of voluntary contraction and of unloading suggest that inhibition and resetting of the tremor can be attributed to the autogenic mechanism induced by Ib fibres discharges. The presence of a rhythmic inhibition in the cycle of Parkinsonian tremor accounts for the longer duration of the inhibitory phase. In practice, these techniques aid the diagnosis of tremor in these two conditions, for example they assist the identification of low frequency essential tremor and of postural tremor in Parkinson's disease.     

Role of the midbrain central gray substance in the performance of a conditioned reflex

The conditional placing reflex was studied in chronic experiments on cats. Neuronal activity of the midbrain periaqueductal grey matter was recorded under conditions of extinction, differentiation and conditional inhibition. Neuronal reactions preceded the conditioned and voluntary movements by 400-800 ms and lasted for 1-2 s in 69 units from total numbers 182 (36.7%). This reactions appeared 200 ms earlier than corresponding neuronal reactions of the motor cortex. 58 neurons (30.9%) were excited by auditory stimuli with latencies 10-50 ms for 2-6 s. 19 neurons (10.1%) were activated by auditory stimuli and conditioned movement. Responses to isolated auditory stimulation were absent in 42 neurons (22.3%), but some of the neurons showed long-lasting (minutes) changes of the background activity under repeated conditioned stimulation. The extinction, differentiation and conditioned inhibition caused specific changes in activity of different neuronal groups. A conclusion is made that the periaqueductal grey matter participated in reflex performance as well as in its inhibition. The functional independence of the first and second neuronal groups in extinction and restoration of conditional reflex is shown.     

Non-dominant eye responses in the dorsal lateral geniculate nucleus of the cat: an intracellular study

While binocularity has been established as an important characteristic of cat visual cortical neurons, neurons in the dorsal lateral geniculate nucleus (LGNd) are commonly believed to be monocular. To test whether binocularity exists at the level of the LGNd, postsynaptic potentials (PSPs) of 101 cells were intracellularly recorded in eight normal and eight monocularly deprived cats while presenting stimuli to either the dominant or non-dominant eyes. The results showed that: (1) About 92% of neurons (45 out of 49) responded to a flashing spot presented to the non-dominant eye. In contrast to the dominant eye responses, the non-dominant eye PSPs usually exhibited the same polarization tendency (hyperpolarization or depolarization) to flashing spot stimuli of light increment or decrement, and most of them were inhibitory (hyperpolarization, 35 out of 45, 78%). (2) The response field (RF) of the non-dominant eye overlapped that of the dominant eye. (3) For most binocular cells, peak-to-peak amplitudes of non-dominant eye PSPs were about half the size (46%) of those of the dominant eye. The peak latencies and half-peak latencies of non-dominant eye PSPs were significantly longer than those of the dominant eye (mean differences were 5.4 ms and 5.6 ms respectively). (4) Most of the binocular cells responded well to contrast reversing gratings presented to the non-dominant eye, and the responses were clearly spatial-frequency tuned. No null phase could be found for non-dominant eye PSPs, no matter the neuron was classified as X or Y type according to dominant eye elicited responses. Some of the cells responded well to drifting gratings presented to the non-dominant eye. (5) We also recorded 52 cells in monocularly deprived cats, and found that 49 cells (94%) showed significant responses to flashing spots presented to the non-dominant eye, a similar percentage to that found in normal cats (92%). CONCLUSION: as strongly monocular neurons, most of LGNd cells could also be driven by the non-dominant eye. The responses evoked by non-dominant eye stimulation differ greatly from those evoked by dominant eye stimulation, and remain intact even without visual experience. These observations suggest an important role of the perigeniculate nucleus in providing binocular inputs to LGNd cells.     

Tectal afferents monosynaptically activate neurons in the pigeon isthmo-optic nucleus

Postsynaptic responses of 105 neurons in brain slices were intracellularly recorded from the isthmo-optic nucleus (ION) in pigeons, and 18 of these neurons were labeled with Lucifer yellow. Excitatory postsynaptic potentials (EPSPs) or spikes were produced in 93 cells, inhibitory postsynaptic potentials (IPSPs) in 10 cells, and EPSPs followed by IPSPs in two cells following electrical stimulation of the tecto-isthmooptic tract. The EPSPs occurred in an all-or-none fashion, with short latencies (1.3 +/- 0.6 ms). Repetitive stimulation increased their amplitude and duration, demonstrating that temporal summation was involved. Neurons producing excitatory responses were distributed throughout cellular layers of the nucleus. Pure IPSPs had a latency of 3.9 +/- 2.3 ms, and cells that responded in this manner were only distributed in the rostral portion of the nucleus. In the remaining two cells with EPSP-IPSP responses, the latency of excitatory responses was 1.5 ms in one cell and 1.4 ms in the other, and that of inhibitory responses was, respectively, 5.1 and 4.1 ms. Thus, it appeared that excitation was monosynaptic, whereas inhibition may be polysynaptic. Four single injections resulted in dye-coupled labeling, and two pairs of closely apposed cells fired spikes, probably resulting from spatial summation of their excitatory responses. The present study suggests that tectal cells directly activate ION neurons and that tectal fibers contact isthmo-optic neurons in a one-to-one fashion. Taken together with previous studies, it appears that the entire tecto-ION-retinal pathway is excitatory.     

Reactions of neurons of the reticular and ventral anterior thalamic nuclei to electrical stimulation of the centrum medianum of the thalamus

Responses of 145 reticular (R) and 158 ventral anterior (VA) thalamic neurons to electrical stimulation of centrum medianum (CM) were studied in cats anaesthetized with thiopental sodium (30-40 mg/kg intraperitoneally) and immobilized with d-tubocurarine (1 mg/kg). 4.1% of R and 4.4% of VA neurons under study responded to CM stimulation by antidromic spike (latency 0.3-2.0 ms). The conduction velocity of antidromic excitation in axons of those neurons was found to be 1.7-7.6 m/s. There were neurons which responded by antidromic spike to the other thalamic nuclei stimulation as well as to CM. This fact is the electrophysiological proof of the axonal branching in these neurons. 53.8% of R and 46.9% of VA neurons responded to CM stimulation with orthodromic excitation. Two groups of cells were separated among neurons excited orthodromically. The first group neurons responded to CM stimulation by discharges composed of 6-12 spikes with frequency of 130-640 per second. The neurons of the second group generated a single spike. Inhibitory reactions were noticed only in 0.7% of R and in 4.4% of VA neurons. It is shown that afferent impulses from relay nuclei, lateral posterior nucleus and motor cortex converged to some R and VA neurons responding to CM.     

Monosynaptic inhibitory postsynaptic potentials of cerebral cortex neurons]

The auditory cortes of cats immobilized with d-tubocurarine was stimulated by monopolar macroelectrodes (tip diameter 100 mu) or micloelectrodes (tip diameter 100--15 mu). In both cases in cortical neurons located closely to the stimulation point IPSPs were recorded with latencies ranging between 0.4--1.2 and 1.4 6.0 ms. It is suggested that IPSPs of the first group are generated in response to direct stimulation of the bodies and axons of the inhibitory cortical neurons (monosynaptically). The amplitude of such IPSPs ranged in different neurons from 3 to 15 mV and their duration was between 4 and 15 ms. Many of them were complicated by later additional inhibitory volleys. 1.5% of all IPSPs generated in response to geniculocortical fibres stimulation had latencies between 0.8--1.3 ms. It is suggested that these IPSPs were also evoked monosynaptically.     

The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes

Extracellular recordings were made from 94 neurons located in the ventrolateral medulla (VLM) whose firing rate was affected by vestibular nerve (VN) stimulation; 50 of these units were in the subretrofacial (SRF) nucleus, which contains cells that make direct excitatory connections with sympathetic preganglionic neurons. The sample included 12 SRF cells which were antidromically driven from the upper thoracic spinal cord and had conduction velocities of 10 m/s or less; the effect of VN stimulation on all but one of these units was inhibition. The onset latency of the response to VN stimulation was long [20.3 +/- 3.7 (S.E.M.) ms, n = 9, for the antidromically activated neurons and 12.1 +/- 1.2 ms, n = 73, for the others], suggesting that the effects were predominantly polysynaptic. In addition, most of the spontaneously active units tested (33/36) received convergent inputs from the carotid sinus nerve (CSN), as would be expected for neurons which influence sympathetic outflow. Vestibular-elicited inhibition of SRF neurons with projections to the intermediolateral cell column could account for late, long duration inhibition of sympathetic discharges produced by labyrinth stimulation.     

Inhibition in association cortex neurons upon direct and transcallosal stimulation in the cat

The experiments were performed on cats immobilized with myorelaxants. Depression of background activity or IPSP was recorded in neurons of the associative cortex in response to direct cortical and transcallosal stimulation. With the intensification of stimulation the duration of inhibition increased up to a certain limit for each studied cell. After this it still could increase if the number of the stimuli increased. Prolonged inhibition (up to several seconds) in response to a series of stimuli had the same nature as short inhibition about 20 ms evoked by a single stimulus. It was due to a prolonged hyperpolarizing postsynaptic potential. A suggestion is made that neurons producing monosynaptical inhibition in the associative cortex cells can be situated in the contralateral hemisphere.