Somatosensory cortical unit responses during avoidance conditioning to sound

Unit responses of the primary somatosensory cortical-projection area were recorded in cats with established conditioned avoidance to sound during the conditioned response. Five types of changes in unit activity were distinguished during the conditioned reflex. The responses were 400–1000 msec in duration; their time of onset coincided with that of the expected reinforcing stimulus. As a rule the change in unit activity was preceded by changes in the electromyogram of the corresponding limb muscles. Among neurons responding to the conditioning stimulus, the proportion with a short latent period of response to electrical stimulation of the skin was less than during investigation of ordinary unit responses to the same stimulus.     

Repetitive microstimulation alters the cortical representation of movements in adult rats

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 microns. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.     

Dynamics of auditory cortical unit responses of the waking cat during defensive conditioning to acoustic stimulation

In chronic experiments on cats unit responses of the primary auditory cortex (area 50) were studied by microelectrode recording during defensive conditioning to sound. During formation of the reflex biphasic responses with relatively short-latency (50–100 msec) and longer-latency (400–500 and 800–900 msec) activation predominated. Neighboring neurons, whose activity was recorded by the same microelectrode, also were involved more intensively in activity. Application of a differential stimulus in 70% of cases produced definite changes in unit activity, among which responses of activation type predominated. Analysis of the course of spike responses of the same neuron during the period of action of a large number of combinations and its comparison with the formation of the conditioned-reflex motor response revealed no direct correlation between these events.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 2, pp. 99–108, March–April, 1979.     

Somatosensory cortical unit responses in the waking cat to afferent stimuli

Extracellular and intracellular responses of 183 neurons in the primary projection area of the somatosensory cortex to electrical and tactile stimulation of the skin on the contralateral fore limb and to stimulation of the ventro-posterolateral thalamic nucleus of the ipsilateral hemisphere were studied in chronic experiments on cats. Spike responses to afferent stimuli are subdivided into three types: initial with a latent period of under 60 msec; initial followed by late responses with a latent period of over 60 msec; late with a latent period of over 60 msec. In addition another group of neurons responding to peripheral stimuli in the interval between the initial and the late response was identified. In nearly all cases the initial responses to peripheral stimulation had the form of a series of spikes, unlike responses to thalamic stimulation. It is concluded from the durations of the latent periods of these responses that about 70% of neurons in the primary projection area are activated mono- and disynaptically in response to peripheral stimulation; consequently, the intracortical spread of excitation in this zone is restricted.     

Operant conditioning of cortical steady potential responses in rats

This study was conducted to determine if amplitudes of rat corticol steady potential (SP) response to an auditory stimulus could be altered by operant conditioning procedures using food reinforcement. The negative SP responses to the 5-sec tone alone diminished with repeated presentation of the stimulus. When food reinforcement was given immediately following the tone, SP response amplitudes increased and stabilized after 4–5 sessions. Thereafter, the animals were required to increase or decrease the amplitudes of response in order to obtain reinforcement. Two of three rats required to increase amplitudes were successful and three of four rats required to decrease amplitudes were successful. It is concluded that changes in cortical SP responses can be operantly conditioned.     

Biochemical and functional responses stimulated by platelet-activating factor in murine peritoneal macrophages

Platelet-activating factor (PAF) is a potent stimulant of leukocytes, including macrophages. To analyze the mechanisms of its effects upon macrophages, we determined whether macrophages bear specific surface receptors for PAF. By competitive radioactive binding assays, we determined two classes of specific receptors to be present on purified membranes derived from murine peritoneal macrophages (one having a Kd of approximately 1 X 10(-10) M and one a Kd of approximately 2 X 10(-9) M). When the macrophages were incubated with PAF, rapid formation of several inositol phosphates including inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate were observed. PAF also elevated intracellular levels of calcium to 290 +/- 27% of basal levels which were 82.7 +/- 12 nM. Increases in calcium were observed first in submembranous areas of the macrophages. PAF also led to increases of 1,2-diacylglycerol of approximately 200 pmol/10(7) cells. A characteristic pattern of enhanced protein phosphorylation, similar to that initiated by both phorbol 12,13-myristate and lipopolysaccharide, was observed and involved enhanced phosphorylation of proteins of 28, 33, 67, and 103 kD. The half-maximal dose of PAF for initiating all the above effects was approximately 5 X 10(-9) M. PAF also initiated significant chemotaxis of the cells; the half-maximal dose for this effect was approximately 1 X 10(-11) M. Taken together, these observations suggest that murine mononuclear phagocytes bear specific membrane receptors for PAF and that addition of PAF leads to generation of break-down products of polyphosphoinositides, subsequent changes in intracellular calcium and protein phosphorylation, and chemotaxis.     

Visual cortical unit responses to photic stimulation of different zones of the receptive fields in cats

In acute experiments on unanesthetized curarized cats the intensity functions, response thresholds, inhibition thresholds, and differential sensitivity of 96 neurons in the primary visual projection cortex were investigated by extracellular recording of unit activity during central and peripheral stimulation of their receptive fields. In darkness the neurons had wide threshold and above-threshold reliefs (3–30°). The threshold reliefs of the receptive fields of some cells were found to be V-shaped, whereas others were marked by alternation of zones of increased and reduced excitability. Sensitivity of both excitatory and inhibitory inputs of the receptive field as a rule was greatest in the center. Inhibitory inputs of different cortical neurons were much more standard and less sensitive to light, and they were mainly activated within the intermediate (mesoptic) range of brightnesses. During light adaptation the threshold contour of the receptive field narrows sharply, mainly because of the fall in sensitivity of its peripheral inputs. Compared with the lateral geniculate body and retina, the relative number of low-threshold elements, sensitivity in the system of inhibitory elements, and differential brightness sensitivity are greater in the cortex. The mechanisms of formation of receptive fields of cortical neurons and their modification during changes in the level of adaptation, and also the role of excitatory and inhibitory inputs of the cell in these effects are discussed.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 227–235, May–June, 1979.     

Reticular meshwork of the spleen in rats studied by electron microscopy

The reticular meshwork of the rat spleen, which consists of both fibrous and cellular reticula, was investigated by transmission electron microscopy. The fibrous reticulum of the splenic pulp is composed of reticular fibers and basement membranes of the sinuses. These reticular fibers and basement membranes are continuous with each other. The reticular fibers are enfolded by reticular cells and are composed of two basic elements: 1) peripheral basal laminae of the reticular cells, and 2) central connective tissue spaces in which microfibrils, collagenous fibrils, elastic fibers, and unmyelinated adrenergic nerve fibers are present. The basement membranes of the sinuses are sandwiched between reticular cells and sinus endothelial cells and are composed of lamina-densalike material, microfibrils, collagenous fibrils, and elastic fibers. The presence of these connective tissue fibrous components indicates that there are connective tissue spaces in these basement membranes. The basement membrane is divided into three parts: the basal lamina of the reticular cell, the connective tissue space, and the basal lamina of the sinus endothelial cell. When the connective tissue space is very small or absent, the two basal laminae may fuse to form a single, thick basement membrane of the splenic sinus wall. The fibrous reticulum having these structures is responsible for support (collagenous fibrils) and rebounding (elastic fibers). The cells of the cellular reticulum--reticular cells and their cytoplasmic processes, which possess abundant contractile microfilaments, dense bodies, hemidesmosomes, basal laminae, and a well-developed, rough-surfaced endoplasmic reticulum, and Golgi complexes, which are characteristic of both fibroblasts and smooth muscle cells--are considered to be myofibroblasts. They may play roles in splenic contraction and in fibrogenesis of the fibrous reticulum. The contractile ability may be influenced by the unmyelinated adrenergic nerve fibers that pass through the reticular fibers. The three-dimensional reticular meshwork of the spleen consists of sustentacular fibrous reticulum and contractile myofibroblastic cellular reticulum. This meshwork not only supports the organ but also contributes to a contractile mechanism in circulation regulation, in collaboration with major contractile elements in the capsulo-trabecular system.     

Myocardial functional preservation during ischemia: Influence of beta blocking agents

To determine whether prior acute Beta blockade protects the heart against the deleterious effects of normothermic low flow global ischemia on myocardial function, aortic pressure, developed pressure, dP/dtmax and end diastolic pressure were monitored in isolated perfused rabbit hearts prior to, during and following 30 and 60 min ischemia, during which either Krebs-Henseleit (control) or Beta blocking agents, Bevantolol (cardioselective) or Propranolol (non-selective) were perfused through the heart. Control hearts made ischemic for 30 min and then reperfused had significantly elevated end diastolic (p < .01) and aortic pressures (p < .01) and reduced developed pressure relative to baseline (p < .05). Hearts treated with Bevantolol or Propranolol (3 × 10^-5 m/l) 5 min prior to and during 30 min ischemia recovered preischemic developed pressure and dP/dt_max (p > 0.05), while end diastolic pressure was elevated (p < .01, p < .05 respectively). Aortic pressure was unchanged relative to baseline (p > .05). Comparison of indices from hearts under Beta blockade with controls showed that following 30 min ischemia and recovery, the Bevantolol treated group had reduced aortic pressure (p < .01) and end diastolic pressure (p < .05) and increased percent developed pressure and percent dP/dt_max (p < .001) relative to control. In the propranolol treated group, end diastolic pressure was reduced and percent developed pressure (p < .01) and percent dP/dt_max (p < .001) were increased relative to unblocked hearts. Following 60 min ischemia and 30 min reperfusion, reduction in all functional indices occurred, however dP/dt_max was unchanged from baseline in the Propranolol and Bevantolol treated groups. Comparison between groups showed that the Bevantolol treated group had significantly better dP/dt_max and developed pressure (p < .05), whereas the Propranolol group shows no significant difference from baseline (p > .05) (K-H). We conclude that following short periods of ischemia, Beta blockade protects the heart from deleterious function effects of ischemia but that the protective effect is diminished in Bevantolol relative to Propranolol treatments following prolonged ischemia. The data indicates that the beneficial effects of Beta blockade in reducing ischemic induced damage occurs early during conditions of ischemia such as would be present in the setting of acute myocardial infarction.     

Evoked activity in the ventral horn of the lumbar segments of the spinal cord during cortical inhibition of cortical motor responses

Electrical activity in the flexor nerve and focal potentials (FP) in the medial and lateral zones of the ventral horn (VH) of segments L₆ and L₇ of the spinal cord, evoked by excitation of the contralateral motor cortex, were recorded in delicate experiments on cats. These focal potentials were studied during inhibition of the flexor response that developed as a result of prior excitation of the ipsilateral cortex ("cortical inhibition"). During the inhibition the FP's of the medial zone (layer VIII, according to Rexed) were greatly increased, mainly in their negative components, their time-characteristics being altered. When the interval between excitations was 50 msec (in that case the inhibition was most pronounced) the medial FP's arose against a negative background, which was a late component of the previous activity evoked by conditioning excitation. The appearance of this late component was correlated with the development of inhibition of the cortical flexor response. At the same time a positive condition developed in the lateral zone, in the region of the nucleus biceps-semitendinosus, which indicated orientation in a lateral direction of the interneurons discharging in the medial zone at late periods after the conditioning excitation. Inhibition of the flexor response was accompanied by depression of the lateral FP's without change in their sign or in the time-structure of their components. It is suggested that cortical inhibition of the cortical flexor response arises at the interneuron level. The functional structure of that inhibitory pathway is discussed.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 3, No. 2, pp. 185–193, March–April, 1971.     

Long-term potentiation and unit evoked responses in the cingulate cortex of freely moving rats

Long-term potentiation (LTP) of synaptic efficacy is considered to be the most probable physiological mechanism of long-term memory. However, lack of understanding of cellular and subcellular mechanisms of LTP induction in freely behaving animals does not correspond to the importance of the problem. It was tested whether the characteristics of potentiation in the cingulate cortex after tetanization of the subiculocingulate tract (SCT) meet the criteria of true LTP (that passes all known stages in its development and lasts for more than a day in freely-behaving animals). Additionally, characteristics of spike responses to SCT stimulation and the effects of application of different glutamate receptor blockers were studied. Without application of GABA receptor blockers, the LTP lasted for more than 24 hours. Application of NMDA glutamate receptor blockers significantly inhibited field potentials evoke by testing stimulation. Short-latency spike responses to SCT stimulation were recorded with low probability that increased with stimulation intensity. The obtained data reveal the possibility to compare the involvement of cingulate neurons in acquisition of adaptive behavior and changes in their spike responses during the LTP development in freely-moving rats.     

Effect of interruption of descending cortical connections on unit responses to extracellular polarization in the lateral geniculate body

Acute experiments on cats showed that unilateral division of projection connections from the cerebral cortex gives rise to definite changes in the effects of extracellular polarization of lateral geniculate neurons: in 40% of cells the regular firing pattern is disturbed in the initial period of action of anodal polarization, the number of cells with after-responses and prolonged changes in spontaneous firing pattern is significantly reduced, and the number of neurons capable of modifying their type of activity under the influence of an incoming polarizing current is also reduced. After interruption of the descending cortical connections the functional characteristics of the lateral geniculate neurons are altered, with a resulting narrowing of the range of their physiological responses to the polarizing current. These facts suggest that the most complex processes of tonic regulation of unit activity in the lateral geniculate bodies require the active participation of the cerebral cortex.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 629–635, November-December, 1972.     

Transient changes of cortical interhemispheric responses after repeated caffeine administration in immature rats

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules - highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 - were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development.     

Assessment of plasma leukotriene and prostaglandin levels during adjuvant arthritis and kaolin-induced paw oedema in rats

Plasma levels of some arachidonic acid metabolites were investigated in acute and chronic models of inflammation in rats. As a model of chronic inflammation, adjuvant arthritis in rats induced by the injection of Freund's complete adjuvant, and as an acute model for inflammation, kaolin-induced paw oedama were used. Plasma leukotriene(LT) C4-like and prostaglandin(PG) E2-like activities were quantitated by bioassay in guinea-pig ileum and rat stomach fundus respectively. In the course of adjuvant arthritis, plasma levels of LTC4- and PGEi2-like activities were increased. Plasma LTC4-like activity reached a maximum within 3 weeks, while PGE2-like activity reached a maximum 10 days after adjuvant injection. In the early phase of adjuvant arthritis, levels of both LTC4- and PGE2-like activities were found to be low but both activities were increased in the late phase of inflammation.