Oxaloacetate Decreases the Infarct Size and Attenuates the Reduction in Evoked Responses after Photothrombotic Focal Ischemia in the Rat Cortex

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.2 mg/100 g, i.v.). Following induction of the lesion, we measured the infarct size and the amplitudes of the somatosensory evoked potentials (SEPs) as recorded from the skull surface. The photothrombotic lesion resulted in appreciably decreased amplitudes of the evoked potentials, but OxAc administration significantly attenuated this reduction, and also the infarct size assessed histologically. We suggest that the neuroprotective effects of OxAc are due to its blood Glu-scavenging activity, which, by increasing the brain-to-blood Glu efflux, reduces the excess Glu responsible for the anatomical and functional correlates of the ischemia, as evaluated by electrophysiological evoked potential (EP) measurements.     

Physiological Changes during Recovery from a Primate Dorsal Column Lesion

The evoked potential (EP) over primary somatosensory cortex (SI) was monitored before and after a complete lesion of the primate dorsal column (DC) pathway on one side. The EP was elicited by electrocutaneous or mechanical stimulation of either foot, and was recorded from the contralateral cortical surface for periods of up to 3 months after the lesion. The amplitudes of the three major peaks (P20, N50, and P90) of the cortical somatosensory EP were significantly reduced following interruption of the contralateral DC. Over weeks following the lesion, there was a significant increase in amplitude of the P90 component of the EP that was not evident in the other peaks. The postlesion increases in P90 amplitude were correlated with improved performance on a task that required grasping with either foot, suggesting that behavioral recovery from a DC lesion results in part from neural plasticity, as opposed to a simple relearning of the task.     

Concentration- and time-dependent effect of aminooxyacetic acid on cortical epileptogenicity

In the present electrophysiological study the effect of aminooxyacetic acid (AOAA) on the cortical epileptogenicity, and on the basic electro-cortical activity was investigated in anesthetized rats. AOAA did not induce spontaneous epileptiform discharges but modified the somato-sensory evoked responses and the cortical epileptogenicity (induced by 4-aminopyridine) in the same manner depending on its concentration. AOAA at low concentrations increased the amplitude of evoked responses and the ipsilateral manifestation of epileptiform activity, however, at high concentrations significantly suppressed both the evoked responses and the induction and expression of seizures discharges. The anticonvulsive effect of AOAA was time-dependent (reached its maximum after 2h AOAA pre-treatment) and reversible. AOAA at low concentrations probably increases the efficacy of the NMDA excitatory system and decreases GABA-synthesis, resulting neuronal hyperexcitation. However, AOAA at high concentrations can lead to an effective cortical inhibition through intra- and extracellular accumulation of GABA. The gradual GABA accumulation - up to a certain level - at the synapses could also explain the time-dependency of the anticonvulsive effect of AOAA.     

Effects of Stimulation of the Periaqueductal Gray and <Emphasis Type="Italic">Locus Coeruleus</Emphasis> on Postsynaptic Reactions of Cat Somatosensory Cortex Neurons Activated by Nociceptors

In cats, we studied the influences of stimulation of the periaqueductal gray (PAG) and locus coeruleus (LC) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulations of the infraorbital nerve and ventroposteromedial nucleus of the thalamus) afferent inputs. Twelve cells activated exclusively by nociceptors and 16 cells activated by both nociceptive and non-nociceptive influences (hereafter, nociceptive and convergent neurons, respectively) were recorded intracellularly. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the latter, of significant duration, up to 200 msec) complex. Electrical stimulation of the PAG (which could itself evoke activation of the cortical neurons under study) resulted in long-term suppression of synaptic responses evoked by excitation of nociceptors (inhibition reached its maximum at a test interval of 600 to 800 msec). We observed a certain parallelism between conditioning influences of PAG activation and effects of systemic injections of morphine. Isolated stimulation of LC by a short high-frequency train of stimuli evoked primary excitatory responses (complex EPSPs) in a part of the examined cortical neurons, while in other cells high-amplitude and long-lasting IPSP (up to 120 msec) were observed. Independently of the type of the primary response to PAG stimulation, the latter resulted in long-term (several seconds) suppression of the responses evoked in cortical cells by stimulation of the nociceptive inputs. The mechanisms of modulatory influences coming from opioidergic and noradrenergic brain systems to somatosensory cortex neurons activated due to excitation of high-threshold (nociceptive) afferent inputs are discussed.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 61–73, January–February, 2005.     

Responses of the neurons of the cortical secondary auditory area to acoustic and non-acoustic stimuli in cats

The responses of the cortical secondary auditory area (AII) to the non-acoustic stimuli (electrical stimulation of the skin in the vibrissae area and light flash) and their combination with acoustic stimulation (sound click or tone) were studied in experiments on cats anesthetized by kalipsol using extra- and intracellular recording. Of the total number of neurons, 69% of the units generating spike responses to the acoustic stimulation responded to the non-acoustic stimulation too. The responses to the modal-nonspecific stimulation, as a rule, were weak and variable; they were mostly represented by a tonic change in the neuronal discharge frequency. The nonspecific stimulation evoked primary excitatory and inhibitory postsynaptic potentials in 77% and 20% of the examined neurons, respectively. We found that synaptic effects of the nonspecific and specific stimulations interact with each other, ensuring considerable modulation of the latter (mostly a significant facilitation resulting from the EPSP summation and suppression of an inhibitory component of the response to acoustic stimulation). Possible participation of the midbrain reticular formation in the transmission of the modal-nonspecific influences to the cortical neurons is considered; stimulation of this structure evoked responses similar to those evoked by the modal-nonspecific sensory stimuli.Neirofiziologiya/Neurophhysiology, Vol. 26, No. 5, pp. 356–364, September–October, 1994.     

Effect of picamilon on inhibitory postsynaptic responses of cortical neurons

In experiments on immobilized anesthetized rats, we intracellularly recorded neuronal responses in the motor cortex before and after application of picamilon (PM) on the cortical surface; the responses were evoked by intracortical stimulation. Aplications of PM in the 5, 20, 50, and 100 μM concentrations noticeably increased, while that in the 10 μM concentration decreased the amplitude of IPSP in the cortical neurons. Probable mechanisms of the effect of PM on a cellular level are discussed.     

Auditory cortex basal activity modulates cochlear responses in chinchillas

Background

The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system.

Methodology/Principal Findings

Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses.

Conclusions/Significance

These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea.     

Spontaneous and evoked activities of interpositus nucleus neurons before and after lesion of the cerebellar cortex

Spontaneous and evoked activities of nucleus interpositus neurons (IN) of the cerebellum were examined before and after cerebellar paravermal cortex lesions in cats anesthetized with alpha-chloralose. It was found that spontaneous activity increased dramatically following cortical ablation: before the lesion only 4% of cells encountered fired at a rate exceeding 80 impulses/sec., whereas up to 40% discharged at this rate postoperatively. Responses to paw stimulation were also altered: the initial excitation was lengthened from 8.5 to 15.8 msec; narrow; trough causing segmentation in this excitation, which seems to result from Purkinje cell inhibition, was absent; and the succeeding inhibitory period was reduced in duration by 50%. Also after the lesion there was a strong tendency for the neurons to discharge in bursts. It is suggested that changes in cell activity in the IN following cortical lesion unveil neural mechanisms of motor disturbances in lesioned cats.     

A comparison of forepaw and vibrissae somatosensory cortical evoked potentials in the rat

Somatosensory evoked potentials were elicited in anesthetized rats by electrical stimulation of the forepaw (F-SEP) or the vibrissae (V-SEP) and were compared in order to study which of these is more valid animal model for studying the physiology and pathophysiology of somatosensory evoked potentials (SEPs) that are often recorded in man in a clinical setting. Intensity and rate functions were measured for the two potentials. The V-SEPs had larger amplitudes than the F-SEPs at high stimulus intensity and low stimulus rate. Furthermore, the ratios of the maximal amplitude of the F-SEP to that of the V-SEP (0.66) and of the areas under the curves of the two responses (0.75) reflected the smaller representation of the forepaw in the primary somatosensory cortex of the rat, compared to the vibrissae (ratio of cortical areas about 0.79). The differences should be taken into account when using median nerve SEP in the rat as a model of the human SEP. Study of V-SEPs in rat may provide insight into trigeminal nerve SEPs in man, which are also occasionally used for neurological evaluation.     

Astroglia demonstrate regional differences in their ability to maintain primary dendritic outgrowth from mouse cortical neurons in vitro

To determine whether glia from different regions of the central nervous system (CNS) initiate or maintain primary dendritic growth, embryonic day 18 mouse cortical neurons were co-cultured with rat (postnatal day 4) astroglial cells derived from retina, spinal cord, mesencephalon, striatum, olfactory bulb, retina, and cortex. Axon and dendrite outgrowth from isolated neurons was quantified using morphological and immunohistochemical techniques at 18 h and 1, 3, and 5 days in vitro. Neurons initially extend the same number of neurites, regardless of the source of glial monolayer; however, glial cells differ in their ability to maintain primary dendrites. Homotypic cortical astrocytes maintain the greatest number of primary dendrites. Glia derived from the olfactory bulb and retina maintained intermediate numbers of dendrites, whereas only a small number of primary dendrites were maintained by glia derived from striatum, spinal cord, or mesencephalon. Longer axons were initially observed from neurons grown on glia that did not maintain dendrite number. Axonal length, however, was similar on the various monolayers after 5 days in vitro. Neurons that were grown in media conditioned by either mesencephalic or cortical glia for the first 24 h followed by culture media from glia of the alternate source for 4 days in vitro confirmed that glia maintained, rather than initiated, the outgrowth of the primary dendritic arbor. These results indicate that glial cells derived from various CNS regions differ in their ability to maintain the primary dendritic arbor from mouse cortical neurons in vitro. © 1995 John Wiley & Sons, Inc.     

Effects of hypothermia on auditory brain-stem and somatosensory evoked responses. A model of a synaptic and axonal lesion

Auditory nerve brain-stem (ABR) and somatosensory evoked responses (SER) were recorded in cats as body temperature was uniformly lowered from 37 to 27°C. Analysis of the results showed that the alterations in the evoked responses were due to disturbances induced both in axonal propagation and synaptic transmission by the hypothermia. By studying the first wave of the SER, which is solely an axonal event, and by assuming reasonable values for the total synaptic delay and axonal propagation times along the ABR pathway, it was concluded that this lesion model induced an effect on synaptic transmission 1.3–1.7 times greater than that on axonal propagation. There was a strong inverse correlation between wave latency and body temperature, with slightly steeper slopes for the longer latency waves. Wave amplitudes were not correlated with temperature. Furthermore, the wave latencies and amplitudes were generally not dependent on stimulus rate.     

Postsynaptic Reactions in Somatosensory Cortex Neurons Activated by Stimulation of Nociceptors: Modulation upon Stimulation of the Central Grey, <Emphasis Type="Italic">Locus Coeruleus</Emphasis>, and <Emphasis Type="Italic">Substantia Nigra</Emphasis>

In experiments on cats, we studied the effects of electrical stimulation of the cerebral central grey (CG), locus coeruleus (LC), and substantia nigra (SN) on postsynaptic processes evoked by nociceptive volleys in somatosensory cortex neurons. Nineteen cells activated exclusively by stimulation of nociceptors (intense stimulation of the dental pulp) and 26 cells activated by both nociceptive and non-nociceptive (near-threshold) stimulations of the n. infraorbitalis and thalamic nucl. ventroposteromedialis (VPM) were intracellularly recorded (nociceptive and convergent cortical neurons, respectively). In neurons of both groups, stimulation of both nociceptive afferents and the VPM evoked complex responses having on EPSP-spike-IPSP patterns (duration of IPSPs about 200-300 msec). Electrical stimulation of the СG, which per se could activate the examined cortical neurons, induced prolonged suppression of synaptic responses evoked by stimulation of nociceptors; maximum inhibition was observed at 600- to 800-msec-long conditioning–test intervals. A certain parallelism was observed between the conditioning effects of СG stimulation and effects of systemic introduction of morphine. Isolated stimulations of the LC and SN by short high-frequency pulse series evoked primary complex EPSPs in a part of the examined cortical neurons, while high-amplitude IPSPs (up to 120 msec long) were observed in other units. Independently of the type of the primary response, conditioning stimulations of the LC and SN induced long-lasting (several seconds) suppression of synaptic responses evoked in cortical neurons by stimulation of nociceptive inputs. Mechanisms of modulating influences coming from opioidergic, noradrenergic, and dopaminergic cerebral systems to neurons of the somatosensory cortex activated upon excitation of high-threshold (nociceptive) afferent inputs are discussed.     

Facilitating action of medial prefrontal cortex upon the noxious thermally-evoked responses in thalamic centralis lateralis nucleus.

This paper shows a medial prefrontal cortex (CxAP9) facilitating influence upon the unit activity of the centralis lateralis (Cl) nucleus of the thalamus, in rats anesthetized with urethane. Cortical influences were studied using both cortical cooling and cortical spreading depression (CSD) procedures. Both spontaneous and noxious thermally evoked activities were considered. When CSD was propagated and affected the CxAP9, as well as during the cooling of this area, both spontaneous activity and the responses evoked in Cl cells by noxious stimulation were blocked. This effect was interpreted as a cortical disfacilitation upon Cl cells. During the cortical silent period we tested the excitability of a few Cl cells, provoking their activation by passing electrical current across the same Cl recording electrode. No changes were observed in their excitable response threshold during CSD or cortical cooling. Our results are in agreement with the proposition of a tonic cortical facilitatory action upon the spontaneous and noxious-evoked responses recorded in the Cl cells.     

Cold‐ and menthol‐evoked membrane potential changes in the moss Physcomitrella patens: influence of ion channel inhibitors and phytohormones

Microelectrode measurements carried out on leaf cells from Physcomitrella patens revealed that a sudden temperature drop and application of menthol evoked two types of different‐shaped membrane potential changes. Cold stimulation evoked spike‐type responses. Menthol depolarized the cell membrane with different rates. When it reached above 1 mV s^?1, the full response was recorded. Characteristic for the full responses was also a few‐minute plateau of the membrane potential recorded after depolarization. The influence of inhibitors of calcium channels (5 mM Gd³⁺), potassium channels (5 mM Ba²⁺), chloride channels (200 μM Zn²⁺, 50 μM niflumic acid) and proton pumps (10 μM DES), an activator of calcium release from intracellular stores (Sr²⁺), calcium chelation (by 400 μM EGTA) and phytohormones (50 μM auxin, 50 μM abscisic acid (ABA), 500 μM salicylic acid) on cold‐ and menthol‐evoked responses was tested. Both responses are different in respect to the ion mechanism: cold‐evoked depolarizations were influenced by Ba²⁺ and DES; in turn, menthol‐evoked potential changes were most effectively blocked by Zn²⁺. Moreover, the effectiveness of menthol in generation of full responses was reduced after administration of auxin or ABA, i.e. phytohormones known for their participation in responses to cold and regulation of proton pumps. The effects of DES indicated that one of the main conditions for generation of menthol‐evoked responses is inhibition of the proton pump activity. Our results indicate that perception of cold and menthol by plants proceeds in different ways due to the differences in ionic mechanism and hormone dependence of cold‐ and menthol‐evoked responses.     

The effect of stimulation of the deep layers of somatosensory zones CI and CII on the activity of motor zone MI of the cat cortex]

The influence of electrical stimulation of deep layers of the somatosensory zones CI and CII on unit responses and intercortical evoked potentials (IEP) in the motor cortical zone MI in projection areas of the anterior contralateral limb was studied in cats anaesthetized with Nembutal and immobilized with diplacine. Latencies of the main IEP components and their different behaviour during repeated stimulation, experimental hypoxia and Nembutal administration suggested the presence of intercortical connections of an oligo- and polysynaptic nature. Only 22% of the MI zone units proved to be responsive to CI and CII stimulation; the latencies of the unit discharges varied from 4.3 to 35 msec. A relatively smaller effectiveness of short-latency inputs from CI and CII to MI was recorded as compared with long latency ones.     

Response component analysis of simple and complex cells of area 18 during depression of area 17.

Simple and complex cells of visual areas of cats may be reliably classified according to the modulatory index (MI) of their responses. This investigation is aimed at analysing the MI in area 18 when a small region (about 200-400 microm in diameter) of area 17 was inactivated with a microinjection of GABA, in anesthetized cats. Cells were stimulated with sine-wave gratings whose orientation, spatial, and temporal frequencies were optimal for the studied unit. The AC and DC response components, and the MI were computed along with fast Fourier transforms of evoked discharges recorded as peristimulus time histograms. Results showed that these response components were relatively unaffected in simple cells, whereas complex cells exhibited large changes when area 17 was silenced. In particular, a large proportion of complex cells showed a MI greater than 1, thereby adopting a response pattern resembling simple cells. It is suggested that this subpopulation of complex cells receives a direct input from geniculate X cells.     

Morphological and electrophysiological consequences of unilateral pre- versus postganglionic vestibular lesions in the frog

The combined removal of the labyrinthine sense organs and of the ganglion of Scarpa on one side (postganglionic section) resulted in a degeneration of afferent fibres in the eighth nerve of the frog (Rana temporaria) within 2–4 days. If the eighth nerve was sectioned more peripherally (preganglionic section) and its distal part was removed together with the labyrinthine organs degeneration of afferent fibres was absent or restricted to very few fibres. Electrical stimulation of vestibular afferents in vitro evoked monosynaptic field potentials in the ipsilateral and via commissural fibres di-and polysynaptic field potentials in the contralateral vestibular nuclei. Afferent-evoked field potentials recorded on the intact side of chronic frogs ( 60 days) with a preor postganglionic lesion and afferent-evoked field potentials recorded on the operated side of chronic frogs with a preganglionic lesion had amplitudes that were very similar to those recorded in control frogs. Commissurally evoked field potentials recorded on the operated side of chronic frogs with preor postganglionic lesions were significantly increased (by about 90%) with respect to control amplitudes. In both groups the time-course of this increase was very similar, started between 15 and 30 days and saturated for survival periods longer than 60 days. Unilateral inactivation of vestibular afferents, but not degeneration, is the likely common denominator of the central process leading to the reported neural changes. A reactive supersensitivity of central vestibular neurons on the operated side for glutamate as a possible mechanism is unlikely, since converging afferent and commissural inputs are both glutamatergic and only one of them, the commissural input, was potentiated. Comparison of the time-courses of neural changes in the vestibular nuclei and postural recovery in the same individuals excludes a causal relation between both phenomena.Abbreviations HL hemilabyrinthectomy - VNC vestibular nuclear complex - HRP horseradish peroxidase - N. VIII eighth nerve - N. IX ninth nerve     

Corticofugal influences on the neurons of different regions of the hypothalamus

Responses of the neurons of the lateral and ventromedial hypothalamic regions (HL andHvm, respectively), as well as of the area of the dorsal hypothalamus (aHd) and the projection region of the medial forelimb bundle (MFB), evoked by stimulation of the proreal cortex (field 8), cingular cortex (field 24), pyriform lobula (periamigdalar cortex), and hippocampus (CA3) were studied in acute experiments on cats under ketamine anesthesia. Distributions of the latent periods of the responses recorded from hypothalamic neurons at stimulation of the above cortical structures were analyzed. The responses were classified into primary excitatory and primary inhibitory. Stimulation of the proreal gyrus evoked four times more excitatory responses than inhibitory responses. With stimulation of the cingular gyrus, the ratio of excitatory/inhibitory responses was 1.5∶1. Stimulation of the pyriform cortex evoked activatory and inhibitory responses with a similar probability. With hippocampal stimulation, inhibitory responses appeared two times more frequently than excitatory reactions. The hypothalamus was found to be a zone of wide convergence: one-half of all responding neurons in theHL andHvm responded to stimulations of two or more tested cortical zones. In 26% of the cells, only excitatory convergence was observed, while in 10% only inhibitory convergence was found; 21% of the cells revealed mixed convergence.     

Effect of neurotropic drugs on cortical evoked potentials

In acute experiments on unanesthetized, curarized cats and rabbits and also on animals anesthetized with chloralose, recordings were made of direct cortical and transcallosal responses, responses in the pyramids of the medulla to peripheral stimulation and stimulation of the motor cortex, primary responses in area S-I, and interzonal somatomotor responses. The effect of narcotics on these cortical responses was shown to persist under conditions partially or completely excluding effects mediated through the reticular formation and other subcortical structures (intracarotid injection of the drugs or their local application to the cortex, experiments after premesencephalic section or on the isolated cortex). Neuroleptics have only a slight effect on these cortical evoked responses, mainly due to their blocking action on the reticular formation. Tranquilizers of the benzodiazepine series are active against the cortical responses studied, and this effect is due to their direct action on the cortex.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 6, pp. 582–591, November–December, 1971.