The role of GABAA and GABAB receptors in formation of evoked potentials in the barrel cortex of rats

By means of local microapplication of GABA, picrotoxin and CGP 52432, different roles of GABAA and GABAB receptors in the geneses of primary and secondary components of evoked potentials in the somatosensory barrel cortex of rats were shown. The authors conclude that the aftereffect rhythmical components of the evoked potentials are caused by the local pacemaker mechanisms based on endogene properties of barrel neurons.     

Effect of stimulation of β adrenoreceptors on conditioned reflex-related spike activity of neurons of the cat somatosensory cortex

Using extracellular recording of impulse activity of pyramidal neurons of the cat somatosensory cortex generated in the course of realization of an operant conditioned reflex, we examined effects of microiontophoretic applications of an agonist of β2 adrenoreceptors, metaproterenol, and of an antagonist of β adrenoreceptors, propranolol, on the frequency of this impulsation. Applications of propranolol induced intensification of both background and reflex-related spiking. The effect of metaproterenol was manifested as moderate intensification of background discharges, a noticeable increase in the frequency of evoked impulsation, and an increase in the latency of impulse reactions. It is supposed that noradrenergic projections to the neocortex intensify neuronal activity via activation of β2 adrenoreceptors and suppress this activity via influencing mostly β1 adrenoreceptors. Such effects of synaptically active agents should probably be taken into account in the treatment of neurological diseases, namely epilepsy, neurodegenerative disorders, psychoemotional shifts, etc., which are accompanied by emotional and cognitive disorders.     

Effect of electroacupuncture on the nature of changes in the activity of neurons in the 2d somatosensory region of the cerebral cortex

Effects of electroacupuncture (EAP) on the character of spontaneous and evoked neuronal impulse activity changes in the second somatosensory area (S2) of the brain cortex by nociceptive and non-nociceptive stimulation were studied in acute experiments on cats. It was demonstrated that EAP changed the character of S2 neurons activity and formed their new functional state. After EAP activity of non-nociceptive neurons were not changed, evoked activity of nociceptive neurons were inhibited. It is suggested, that EAP preferential blocking the protopathic components of the acute pain.     

Dopaminergic modulation of impulse activity of sensorymotor cortex neurons during conditioned reflex

Changes of conditioned impulse reaction of cortical neurons wer studied during microiontophoretic application of agonist and antagonists of glutamate and GABA transmission and their modulation by dopamine. It was shown paradoxal reaction of facilitation of impulse activity during iontophoretic application of ionotropic glutamate antagonist and depressive influences of metabotropic antagonist. Local iontophoretic application of dopamine increased background and evoked impulse activity of pyramidal neurons of deep layers of cortex and eliminated inhibitory influences of glutamate metabotropic antagonist MCPG. It is concluded that DA has stabilizing effects on activity of cortical neurons. It is suppose that these effects of DA realize through system of inhibitory interneurons.     

Organization of the Connections between the Parietal Associative Zone and the Primary Sensory Zones in the Cat Neocortex

In acute experiments on cats, we studied the impulse activity of 262 neurons of the parietal associative zone (PAZ, field 5). Among them, 129 cells [100 silent units and 29 units generating background activity (BA)] were identified as output neurons, while 133 cells with the BA were interneurons of the intrinsic cortical neuronal circuits. Electrical stimulation of the primary visual, auditory, or somatosensory cortices evoked no impulse responses in silent output PAZ neurons, while output neurons with the BA and interneurons (more than 65 and 80% of the cell units, respectively) generated clear responses (more frequently, phasic). Stimulation of the auditory and visual cortices exerted mostly inhibitory effects, while stimulation of the somatosensory cortex provided mostly excitatory influences. The ratios of neurons generating primary excitatory and inhibitory responses to stimulation of the visual, auditory, and somatic cortices were 0.3:1, 0.6:1, and 3.2:1, respectively. More than 95% of the field-5 neurons were influenced from the primary sensory zones via di- and/or polysynaptic pathways. Monosynaptic excitatory inputs from the visual cortex were identified for 3.8% of interneurons and 6.9% of output PAZ neurons; for the auditory cortical inputs, the respective figures were 1.7 and 3.5%. Monosynaptic connections with the somatic cortex were found only for 4% of the interneurons under study. It has been concluded that interaction of heteromodal signals coming to the PAZ via the corticopetal and associative inputs occurs on neurons of all the cortical layers.     

Nerve growth factor increases stimulus-evoked metabolic activity in acetylcholine-depleted barrel cortex

Lesions of the basal forebrain deplete the neocortex of cholinergic fibers. Acetylcholine depletion in the somatosensory cortex of rats results in reduced stimulus-evoked activity in response to whisker stimulation. Previous studies demonstrate that embryonic basal forebrain transplants improve functional activity toward normal. It is not clear if the activity increase is due to cholinergic replacement or other factors present in the graft. In this study, we examined the possibility that nerve growth factor (NGF), a neurotrophin known as a survival factor and a specific protectant for cholinergic basal forebrain neurons, can preserve basal forebrain cells after a lesion and restore functional activity in the somatosensory cortex. We report that NGF alone is capable of restoring functional activity in the barrel cortex of animals with basal forebrain lesions, while vehicle injections of saline do not alter activity. Both high (10 mug) and low (5 mug) doses of NGF unilaterally injected into the lateral ventricle improved stimulus-evoked functional activity during bilateral whisker stimulation. The mechanism of NGF action is not clear since the restoration of functional activity in cortex was not accompanied by increased cholinergic activity as detected by acetylcholinesterase fiber staining. NGF may act directly on cortical neurons, although its site of action is not well defined.     

Incorporation of neurons of transplants of embryonal rat neocortex in the achievement of sensory function of the cerebral cortex of the recipient

The barrelfield of the adult rats was removed by suction and embryonic tissue of the somatosensory neocortex was transplanted into the cavity. Spontaneous and evoked activity of the grafted neurones was investigated extracellularly 2-3 months after the grafting. The light microscopy of the grafts revealed the presence of normal neuronal cells, but their distribution was diffuse, and they were not organized into barrels as in intact neocortex. The background activity of grafted neurones depended upon the level of the recipient's anaesthesia. The response types of the grafted neurones to vibrissae deflection and to tactile stimulation of the host body surfaces, their latencies and lability did not differ from such of the intact somatosensory cortex, but the receptive fields of the grafted neurones were larger. There was also substantial convergence of inputs from other surfaces upon the grafted neurones. The effectiveness of stimulation of the various skin areas was determined by the proximity of their neocortical representations to the graft.     

Slow potentials and spike unit activity of the cerebral cortex of rabbits exposed to microwaves

Unanesthetized rabbits exposed to 12.5-cm microwaves at a field intensity of 40 mW/cm2 in the region of the head showed an increase in the number of slow waves and spindle-shaped firings in the EEG and a change in the discharge frequency of neurons in the visual cortex in 41-52% of the cases. An enhancement of the evoked response of visual cortex neurons to light was observed in 61% of the cases and a facilitation of the driving response in 80% of all cases. It is concluded that the evoked response is a more sensitive indicator of the microwave effect than background activity. The effects of the fields were most distinctly observed with the driving response.     

Neuronal responses of the rate somatosensory cortex transplanted into the vibrissae representation field of the neocortex to the electrical stimulation of the recipient brain

Neuronal responses of the rat somatosensory cortex grafted into damaged host barrel field to electrical stimulation of the host brain were investigated extracellularly in rats under light pentobarbital anaesthesia. The following structures of the host brain were stimulated: ventrobasal complex and posterior thalamic nuclei, ipsilateral area of vibrissae representation in the sensorimotor cortex and contralateral barrel field. Reactivity of the grafted neurones was lower, than in the intact barrel field, but the mean latencies of responses were not significantly different. Stimulation of the thalamic nuclei was more effective than that of the cortical areas both in grafted and intact barrel fields. Posttetanic depression after repetitive stimulation was often observed in the grafts, while posttetanic potentiation was more usual for the intact barrel field. The data show the sources of some functional afferent inputs to the grafts which may be responsible for neuronal reactions to somatosensory stimulation of the host animal.     

Electric responses of the cerebral cortex to central excitation and inhibition

An attempt was made to evaluate critically the extent to which the background electrocorticogram, neuronal impulse activity, and evoked potentials reflect the state of cortical excitation and inhibition. It was shown that during electrocorticogram desynchronization, firing neurons predominated in the surface (mainly afferent) layers, while inhibited neurons were in the majority in the lower layers of the cortex. Consequently, desynchronization does not reflect diffuse excitation of the cortex and cannot be taken as an index of central excitation. Slow electrocortical waves cannot be used as indicators of an inhibitory state, even though they may be associated with processes leading to the development of inhibition. Under the effects of different stimuli, the number of neurons participating in impulse condition, and the number of neurons temporarily inhibiting impulse activity in the projection cortical area were stable (ratio 2:1). It was found that the correlation between impulse discharges of neuronal pairs increases during both central excitation and central inhibition. Nonetheless, differences between cortical excitation and inhibition were seen in the reorganization of neuronal columns. The use of evoked potentials to determine cortical excitation or inhibition is complicated by the fact that the amplitude of evoked-potential components reflects the divergent influences of many factors. It was shown that conditional excitation diminished the evoked potential to a light stimulus in the projection cortical area, but caused it to increase in the region of the motor analyzer. The elaboration of a conditional inhibition (extinction) is accompanied by the growth of an evoked potential to a stimulus in the primary cortical area, and by its repression in the region of the motor analyzer. In this case, a large delayed negative wave appears in the evoked potential.This report was presented at the All-Union Symposium on Electric Responses of the Cerebral Cortex to Afferent Stimuli, Kiev, October, 1969.Rostov-on-Don State University. Translated from Neirofiziologiya, Vol. 2, No. 2, pp. 140–154, March–April, 1970.     

The neuronal activity of suspension grafts of the neocortex]

Were compared electrophysiological characteristics of suspension (SUS) and solid (SOL) tissue grafts of embryonic neocortex transplanted into the barrel field of adult rats. The level of survival of SUS and SOL grafts did not differ significantly (89% and 95% correspondingly). All SUS grafts were integrated with the host brain judging by histological and electrophysiological criteria. Reactivity of neurons to electrical stimulation of the recipient's brain and to sensory (tactile) stimulation, as well as the latencies of on-responses were similar in both types of the grafts. However, proportion of neurons with on-responses was nearly twice lower in SUS grafts, while the number of neurons responding to tactile stimulation by primary suppression of activity was significantly higher than in SOL ones. It is suggested that the derangement of primary architectonics unavoidable during preparation of suspensions is responsible for the described differences between SUS and SOL grafts.     

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons.

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.     

BOLD signals correlate with ensemble unit activities in rat's somatosensory cortex

Evoked neural activity (ensemble single-unit activity and evoked field potential) and functional magnetic resonance imaging (fMRI) changes of the primary somatosensory cortex in response to electrical stimulation of the hind paw were studied in rats under anesthesia. The effects of stimulation frequency (ranging from 0.3 to 10 Hz) and types of anesthetics (alpha-chloralose and sodium pentobarbital) on blood oxygen level dependent (BOLD) activation and neural activation were compared. Both ensemble single-unit activity and BOLD signal changes achieved maximal activation at 3 Hz of stimulation and responses were significantly stronger under alpha-chloralose anesthesia. The maximal activation of the integral evoked potential (sigmaEP), in contrast, was the highest at 10 Hz; and the values were similar for alpha-chloralose and pentobarbital. These analyses revealed that fMRI image changes were better correlated with ensemble single-unit activity than with sigmaEP during somatosensory stimulations.     

Ontogenesis of the spine-free initial zone of apical dendrites; studies in cortical pyramidal cells of albino rat]

1. In Golgi-Cox-impregnated coronal sections of albino rat brains at 1, 4, 26, 24, 30, 60 and 90 days it is presented the evolution of the spine-less, bare initial zone ("nude zone", NZ) at the proximal apical main dendrites of the layer V pyramidal neurons in the somatosensory and anterior limbie cortex. The quantitative results are analyzed by statistical methods. 2. The NZ is comprehended as a morphological correlate of the endodendritic neuroplasmic flow (Weiss 1944, Globus, Lux and Schuberl 1968, Kreutzberg 1973). The observed changes of the percental frequency and the average length of NZ increases rapidly. 3. The NZ occurs at first in the (12th) 16 postnatal day, thus in a time, when the organs of hearing and the eyes are differentiated completely. Between 16th and 24th day the percental frequency as well as the longitude of NZ increases. During this time the rats will be independent of the mother animals. With the full differentiation of the urogenital tract and especially with the sexual maturity the percentage frequency of NZ increases only at pyramidal cells in the anterior limbie cortex between 24th and 60th day. During 3rd month the NZ is occuring percental more frequently in the anterior limbic cortex than in the somatosensory cortex. At this time the average length of NZ is shorter in the limbic cortex. 4. As to the enriched, vivid movement of the animals and the playing impulse of the young rats the average length of NZ will be extended at pyramidal neurons in the somatosensory cortex during 2nd month, as well as the pattern of spine distribution will be changed along apical dendrites (Schlerhorn, unpublished). During the following (3rd) month the NZ will be shorteded in the somatosensory cortex, obviously caused by new formation of spines at the proximal main dendrites. 5. These newly formed spines in the initial zone of apical dendrites may be inhibitory spines. The inhibitory spines are stained only when using the mercury chromate impregnation according to Golgi-Cox, but not when using the silver chromate methods according to Golgi-Kopsch or Golgi-Bubenaite. The different tingibility of these spines by different Golgi techniques is discussed by Doedens, Nagel and Schierhorn (1974). The pyramidal neurons in the somatosensory cortex possess a longer average length of NZ (Lnz = 7,3[mum]) than the pyramidal cells in the anterior limbic cortex (Lnz = 6.2[mum]). As to NZ the differences between silver and mercury chromate stained pyramidal neurons are greater in the somatosensory cortex than in limbic cortex (see Tab. 7). Therefore we assume that there are in the initial zone of somatosensory pyramidal neurons more inhibitory spines than at the pyramidal neurons in the anterior limbic cortex. 6. The regional differences in the percentual frequency and in the average length of NZ between somatosensory and limbic cortex are new identifying marks of architectonic differentiation of the pyramidal neurons in cortical regions of phylogenetically different ages.     

Interaction between the Dopaminergic and GABA-ergic Systems of the Cortex during Conditioning

Impulse activities were recorded from neurons of the sensorimotor cortex of cats, trained to perform a conditioned placing reaction, before, during, and after iontophoretic application of the synaptically active drugs dopamine (DA) and GABA. Our experiments demonstrated that in most cases isolated application of DA increased the frequency of the impulse activity and the number of spikes related to the placing reaction. On the other hand, GABA evoked decreases in both indexes characterizing the impulse activity. In the case of co-application of DA with GABA, we observed both increases and decreases in the background firing rate activity and in the number of spikes related to the placing reaction. Our results suggest that interaction between the DA-ergic and GABA-ergic systems is realized at the receptor level and cannot be interpreted in an oversimplified manner.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.     

Interaction of influences from the auditory and somatosensory afferent systems on neurons of the primary auditory cortex

In experiments on anesthetized cats, 80 neurons of the primary auditory cortex (A1) were studied. Within the examined neuronal population, 66 cells (or 82.5%) were monosensory units, i.e., they responded only to acoustic stimulations (sound clicks and tones); 8 (10.1%) neurons responded to acoustic stimulation and electrocutaneous stimulation (ECS); the rest of the units (7.4%) were either trisensory (responded also to visual stimulation) or responded only to non-acoustic stimulations. In the A1 area, neurons responding to ECS with rather short latencies (15.6–17.0 msec) were found. ECS usually suppressed the impulse neuronal responses evoked by sound clicks. It is concluded that somatosensory afferent signals cause predominantly an inhibitory effect on transmission of an acoustic afferent volley to the auditory cortex at a subcortical level; however, rare cases of excitatory convergence of acoustic and somatosensory inputs toA1 neurons were observed.     

Cortical potentials evoked by mechanical stimulation of different number of vibrissae of the rat

Distribution maps of cortical potentials evoked by mechanical stimulation of different number of contralateral vibrissae were studied. It was found that stimulation of all the contralateral vibrissae led to more extensive activation than the barrel field in the somatosensory cortex. The activation was most widespread when all the vibrissae were synchronously deflected. With reduction of the number of synchronously stimulated whiskers the activated cortical area did not decrease in parallel. Deflection of only a few whiskers activated significantly smaller cortical areas.     

Electrophysiological Properties of Cultured Sympathetic Neurons of the Rat Superior Cervical Ganglion

We obtained a viable culture of sympathetic neurons of the superior cervical ganglion of neonatal rats. Electrophysiological experiments (patch-clamp in the whole-cell configuration) showed that the cultured neurons generated action potentials after intercellular stimulation by long-lasting pulses of depolarizing current. In some neurons, background impulse electrical activity and evoked postsynaptic currents suppressed by applications of benzohexonium were observed.     

Physiological Slowing and Upregulation of Inhibition in Cortex Are Correlated with Behavioral Deficits in Protein Malnourished Rats

Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD) diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the ‘Gap-crossing’ (GC) task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4) neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3) neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls) and much smaller increase in NMDAR1 (12-20%), suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.