Comparative analysis of morphofunctional features of cortical neurons in ground squirrels and guinea pigs under hypothermia

Activity of sensorimotor cortical neurons in the ground squirrel was studied on slices under cooling the incubation medium from 32–34 to 21–26°С. Hypothermia evoked spontaneous firing activity in “silent” neurons and a slight decrease in firing in high-frequency neurons. Changes in the firing rate arose below 27°С and were accompanied by a fall in the spike amplitude. The intensity of hypothermic and post-hypothermic changes in ground squirrels was lower than in guinea pig sensorimotor cortical neurons recorded under the same conditions. In ground squirrels, most hypothermia-resistant were high-frequency (more than 8 spikes/s) neurons, which accounted for 45% of the recorded, while in guinea pigs high-frequency neurons occurred only in 15% of records. By the diameter of cell bodies, the population of sensorimotor cortical neurons was more homogeneous in ground squirrels than in guinea pigs. It is suggested that specific hypothermic changes in sensorimotor cortical neurons of ground squirrels relate to a lower density of K⁺ channels in their plasma membranes, because in the mammalian nervous system the latter open below 27°С due to thermal limitations of the M-cholinergic reaction which blocks these channels.     

Ensemble activity of neurons in the visual, frontal, and sensorimotor cortices and dorsal striatum during actualization of behavioral program under conditions of strategy choice

Unit and network activity of neurons in the visual, sensorimotor, and frontal cortical areas and dorsal striatum was investigated in cats under conditions of choice of the reinforcement value depending on its delay. The animals did not differ from each other in behavior. After immediate or delayed responses cats got low- or highly-valuable reinforcement, respectively. Single-unit activity in the visual and sensorimotor cortical areas and dorsal striatum was similar during performance of immediate and delayed responses. However, significant inhibition was observed in the frontal neurons during the delay period. The network activity of visual and frontal cortex displayed smaller number of interneuronal interactions during delayed responses as compared to immediate reactions. The network activity of neurons in the brain structures under study pointed to the interstructural interaction, but only during delayed reactions, steady interneuronal communication was observed between the frontal cortex and dorsal striatum. Thus, both types of estimation of cellular activity revealed differences in the ensemble organization during different types of behavior and showed specific reactions of neuronal ensembles.     

Impulse activity of the bulbar cardiovascular neurons during myocardial ischemia and stimulation of the cortical sensorimotor zone

In acute experiments on cats performed under nembutal anesthesia the stimulation of sensorimotor zone in cerebral hemisphere cortex changed the impulse activity of interneurons of bulbar cardiovascular centre and not of the afferent neurons. The analysis of the activity of afferent neurons and interneurons has shown a decrease in coordination between the reaction of these cells to the development of ischemic myocardial lesions during the cortex stimulation. In these conditions bulbar cardiovascular neurons could both increase and decrease the impulse activity. These changes seem to be the reason for the growing incidence of idioventricular ischemic arrhythmias during cortical stimulation.     

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5-C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.     

Effect of a vasopressin analog on the chemoreactive properties of sensorimotor cortex neurons

Subcutaneous injection of 10 micrograms desglycilargininvasopressin (DG-AVP) does not alter the mean frequency of background unit activity of sensorimotor cortical neurons. However, the pattern of impulse activity is essentially changed. At the same time the reactions of sensorimotor cortical neurons to microiontophoretic administration of acetylcholine and noradrenaline experience definite changes. It is suggested that the DG-AVP-induced changes in chemoreactive properties of neurons underlie the effect of this peptide on the learning and memory.     

Function of the superior colliculi of the corpora quadrigemina during creation of a local focus of increased excitability in the mesencephalic reticular formation and sensomotor cortex

In chronic experiments on waking rabbits, the foci of heightened excitability in the sensorimotor cortex and mesencephalic reticular formation affected in a similar way the background neuronal activity in the superior colliculi and that evoked by light stimuli. The effect was manifested in elimination of inhibitory pauses in the neuronal response to light stimulus and in a general increase of discharge frequency. Similarity of the cortical and reticular influences is due to their possible mediation by the same collicular interneurones participating in inhibitory pauses formation in the process of backward inhibition. Increased neuronal activity in the superior colliculi under the action of local foci in the sensorimotor cortex and mesencephalic reticular formation correlated with appearance of forelimb motor reaction to isolated light stimulus testifying to a formation of a functional connection between the visual and motor analyzers. Possible role of the superior colliculi in this process and their participation in the formation of a visually controlled reaction is discussed.     

Modulation of the neuronal activity and evoked potentials of the cerebral cortex by stimulation of the dorsal hippocampus]

In experiments on alert rabbits high frequency stimulation of the CA1 field of the dorsal hippocampus reduced the peak latency of the main negative component of the evoked potential (EP) to a light flash in the sensorimotor and occipital tests areas of the cerebral cortex. A single stimulation of the same part of the hippocampus resulted in a gradually developing facilitation of secondary negativity of the EP 5th component, predominantly in the sensorimotor cortex. Investigation of neuronal responses in the same cortical areas to a stimulation of the CA1 field with different parameters has shown that the effects of EP modulation are due to dynamic reorganizations of cortical neuronal activity.     

Phase relationships of cerebral cortex potentials in the rabbit during the execution of motor responses

EEG waves phase relations in the sensorimotor and visual cortical areas were studied in 12 rabbits before and during a motor reaction in response to light stimulation. Phase relations in the background activity were characterized by a considerable dispersion (from 26 to 45 degrees). Light stimulation increased the quantity of synphasic EEG oscillations in adjacent cortical points and stabilized the phase shift between EEG waves in the sensorimotor and visual cortical areas. Motor reactions of rabbits to light occurred when theta-rhythm with the most constant phase shift was observed in the EEG of these areas.     

GABA metabolism and the formation of a sensorimotor cortex evoked potential in the presence of excess zinc ions

Changes in GABA content, the enzymatic activity of its metabolism and the formation of sensorimotor cortical evoked potential (EP) were studied following long-term ZnCl2 administration. It has been established that a single ZnCl2 injection at a dose of 0.1 and 1 mg/kg was accompanied by an increase in the amplitude of sensorimotor cortical EP, though GABA accumulation in this brain structure was observed. This might account for the prolongation of the period of the potential appearance. Long-term (for 7, 14, 21 days) ZnCl2 administration at a dose of 0.1 mg/kg produced a sharp depression in the potential appearance and an increase in GABA content by 50% with the enhancement of glutamate decarboxylase activity and the attenuation of GABA-transaminase activity.     

Neuronal impulse trains of the visual and sensorimotor areas of the rabbit neocortex in calm wakefulness and pseudoconditioning

The conjugation of unit activity in the neocortical visual and sensorimotor areas during calm wakefulness and in intersignal intervals, in two groups of rabbits at pseudoconditioning was studied. The first group was presented in a random order with flashes and electrocutaneous stimuli, the second one--with sounds and electrocutaneous stimuli. The number of neurones pairs working in correlation during calm wakefulness is significantly less (35%) than during pseudoconditioning (49 and 50% in the first and second rabbits groups, respectively). During calm wakefulness and in both groups during pseudoconditioning, the number of pairs with delays of discharges of the visual area neurones after the sensorimotor one, and of the sensorimotor after visual up to 120 ms was equal. Comparison of the data on delayed neuronal discharges during calm wakefulness and pseudoconditioning with those obtained earlier with conditioned reflexes testifies that forestalling of visual area neuronal discharges by sensorimotor discharges is characteristic only for the activity of cortical projections of conditioned and unconditioned stimuli.     

Effect of precursors and cofactors of nucleic acid and protein synthesis on the response of cortical neurons induced by polarization

Injection of K-orotate and folic acid in different proportions and of vitamine B12 produces changes in the S35-methionine inclusion in the proteins of the sensorimotor cortex, basal ganglia, hypothalamus and hippocampus depending on the proportions of the injected agents. In animals with activation of the synthesis in the brain, surface anode polarization increased the mean frequency of spike activity of the neurones in the sensorimotor cortex and reduced the relative number of units, which responded to polarization by inhibition, as compared with the control animals and those in which no activation of protein synthesis was observed. The characteristics of cortical unit responses to surface anode polarization in experimental rats are apparently due to changes in the chemoreactive properties of their membranes, which set in under the influence of changes in the nucleic acid and protein synthesis in these neurones.     

New insights into Alzheimer's disease progression: a combined TMS and structural MRI study

Background:

Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.

Methodology and Principal Findings:

To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer''s disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.

Conclusions:

In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.     

Activation of glutamate ionotropic connections of sensorimotor cortex neurons during conditioning

Changes in conditioned impulse reactions of neurons in sensorimotor cortex were studied during microiontophoretic application of glutamatergic and GABA ergic agonistic and antagonistic drugs. It was shown that ionotropic glutamate receptors (AMPA and NMDA) are activated by a conditioned stimulus. Not only large pyramidal neurons of deep cortical layers but surrounding short-axon inhibitory interneurons are involved in the reaction. It was shown that the activity of pyramidal neurons is under a constant inhibitory control from surrounding interneurons. This inhibition is involved in organization of excitatory cortical responses during conditioning.     

Hypoactivity Affects IGF-1 Level and PI3K/AKT Signaling Pathway in Cerebral Structures Implied in Motor Control

A chronic reduction in neuromuscular activity through prolonged body immobilization in human alters motor task performance through a combination of peripheral and central factors. Studies performed in a rat model of sensorimotor restriction have shown functional and biochemical changes in sensorimotor cortex. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of Insulin-like Growth Factor 1 (IGF-1), a growth factor known to mediate neuronal excitability and synaptic plasticity by inducing phosphorylation cascades which include the PI3K–AKT pathway. In order to better understand the influence of IGF-1 in cortical plasticity in rats submitted to a sensorimotor restriction, we analyzed the effect of hindlimb unloading on IGF-1 and its main molecular pathway in structures implied in motor control (sensorimotor cortex, striatum, cerebellum). IGF-1 level was determined by ELISA, and phosphorylation of its receptor and proteins of the PI3K–AKT pathway by immunoblot. In the sensorimotor cortex, our results indicate that HU induces a decrease in IGF-1 level; this alteration is associated to a decrease in activation of PI3K-AKT pathway. The same effect was observed in the striatum, although to a lower extent. No variation was noticed in the cerebellum. These results suggest that IGF-1 might contribute to cortical and striatal plasticity induced by a chronic sensorimotor restriction.     

The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Cortico-hippocampal relation of electrical activity during a motor polarization dominant in rabbits

By the method of spectral-coherent analysis, the intercentral relations were studied of the electrical activity of the sensorimotor and premotor cortices and of CAs field of the dorsal hippocampus of both hemispheres during the motor polarization dominant, created by the action of the direct current on the rabbits sensorimotor cortical area. The formation was shown of a new structure of the intercentral relations of electrical activity of the sensorimotor cortex and CA3 of the dorsal hippocampus. It should be noted that the dominant optimum and its inhibition are characterized by different interhippocampal relations: at the optimum a low range of the theta-rhythm is highly coherent while at the activation of "the non-dominant" hemisphere--a high range.     

The participation of the cholinergic system of the rat sensorimotor cortex in regulating different types of movements

To study the role of the cholinergic system of the sensorimotor cortex in regulation of different manipulatory movements and locomotion of Wistar rats, the effects of injections of cholinergic drugs (a cholinergic agonist carbachol and an antagonist scopolamine) into the area of forepaw representation in the sensorimotor cortex on motor activity and performance of manipulatory movements (with prolonged and short pushing) were analyzed. The drugs were injected via special cannulae stereotaxically implanted into the cortex during surgery carried out under Nembutal anesthesia. Carbachol injections (0.03-3 micrograms in 1 microliter of physiologic solution) into the cortex resulted in a significant slowing down of both types of movements as well as an increase in locomotion in the open-field test. Injections of scopolamine (0.3-3 micrograms) into the same cortical area were accompanied by an increase in the number of fast manipulatory movements without significant changes in locomotor activity. The obtained evidence suggests that the cholinergic system of the sensorimotor cortex indifferent manners regulates the innate (locomotion) and acquired movements which require different periods of maintaining the muscle tone of the forepaw (short-time periods for the usual movements necessary for food taking from the narrow horizontal tube and prolonged periods for the learned slow movements with additional tactile and tonic components).     

Modulation of pyramidal response in the rat sensorimotor cortex after combined stimulation of the lateral hypothalamus and the sensorimotor cortex

It was shown during experiments on unrestrained rats that rhythmic stimulation of the pyramidal tract produced a statistically significant increase in the functional activity of neuronal populations of the sensorimotor cortex, manifesting as potentiation of the primary, positive phase of pyramidal cortical response. Combined rhythmically matched stimulation of the pyramidal tract and of the lateral hypothalamus leads to statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response compared with effects produced independently of hypothalamic involvement. When stimulation of the pyramidal tract and the lateral hypothalamus are combined with stimulation applied at the same periodicity to the sensorimotor cortex, a further statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response is seen in addition to the potentiating effect produced by hypothalamic stimulation.Institute for Brain Research of the All-Union Scientific Center of Mental Health, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 367–373, May–June, 1986.     

Coherent analysis of the electrical activity of the rabbit brain during the formation of a motor polarization dominant

By the method of spectral-coherent analysis the dynamics was studied of successive changes in the structure the rabbit brain electrical activity coherent relations in the process of formation of motor polarization dominant created by DC anode action on the sensorimotor cortical region. It has been shown that at earlier stages, when the motor "dominant" reaction is absent, there appears an interhemispheric asymmetry in Coh spectra of electrical activity of the sensorimotor cortex and of the thalamus VPL. On the contrary, interhemispheric asymmetry in Coh spectra of electrical activity of the sensorimotor cortex and dorsal hippocampus CA3 field appears only at the stage when the motor "dominant" reaction is recorded. Asymmetry in alpha- and beta-frequencies ranges in biopotentials Coh spectra of the studied regions coinciding with the motor "dominant" reaction realization is connected with processes of movement organization.     

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

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