Limited plasticity of the rabbit visual cortex and hippocampal neurons in the oddball test

The activity of 41 visual cortex and 20 hippocampal neurons from field CA1 was registered in experiments using oddball-stimulation with different color stimuli varied in intensity. 34% cortical and 37% hippocampal neurons demonstrated plasticity reactions. The significant increase of latest phases of neuronal activity (200-500 and 200-1000 ms after stimulation for cortical neurons and 300-550 ms for hippocampal neurons) was shown in responses to rare deviant stimuli, which had a less intensity than frequently standards. The quantity of the earliest neuronal phase of activity (40-120 ms after stimulation) was stabilized in responses to deviants and standards during the experiment. We propose that such increase of the latest phases of neuronal activity (the limited plasticity) may reflect the mechanisms of orienting reaction.     

Age-specific morphological-functional characteristics of the rabbit's hippocampal neurons during conditioning

Formation of trace rhythm recruitment (an analogue of conditioned time reflex) was studies in CA3 hippocampal neurons of alert young (less than one year), old (54-65 months), and very old rabbits after a prolonged (10-20 min) electro-cutaneous stimulation of a forelimb with the frequency of 0.5-1 Hz. Comparative analysis of neuronal spike activity in young and old rabbits showed that in the late ontogeny the number of spontaneously active neurons was significantly decreased, the proportion of slowly firing neurons increased, the interspike intervals and intervals between spike groups became longer, the number of spikes in a group reduced. The ability of hippocampal neurons to acquire and reproduce the rhythm of the previous stimulation declined with age. No appropriate rhythms were found in neurons of very old animals. A nonspecific increase in neuronal baseline activity was observed in old rabbits after the stimulation. Deterioration of morphological structures of hippocampal neurons and glial cells may explain the impairment of mnestic processes in late ontogeny.     

Aberrant GABA(A) receptor-mediated inhibition in cortico-thalamic networks of succinic semialdehyde dehydrogenase deficient mice

Aberrant γ-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined 'phasic' and 'tonic' GABA(A) inhibition in thalamocortical neurons of somatosensory (ventrobasal, VB) thalamus, nucleus reticularis thalami (NRT) neurons, and layer 5/6 pyramidal neurons of the somatosensory (barrel) cortex of succinic semialdehyde dehydrogenase (SSADH) knock-out (SSADH(-/-)) mice that replicate human SSADH deficiency and exhibit typical absence seizures. We found increased sIPSC frequency in both VB and NRT neurons and larger sIPSC amplitude in VB neurons of SSADH(-/-) mice compared to wild-type animals, demonstrating an increase in total phasic inhibition in thalamus of SSADH(-/-) mice. mIPSCs in both VB and NRT neurons were no different between genotypes, although there remained a trend toward more events in SSADH(-/-) mice. In cortical layer 5/6 pyramidal neurons, sIPSCs were fewer but larger in SSADH(-/-) mice, a feature retained by mIPSCs. Tonic currents were larger in both thalamocortical neurons and layer 5/6 pyramidal neurons from SSADH(-/-) mice compared to WTs. These data show that enhanced, rather than compromised, GABA(A) receptor-mediated inhibition occurs in cortico-thalamic networks of SSADH(-/-) mice. In agreement with previous studies, GABA(A) receptor-mediated inhibitory gain-of-function may be a common feature in models of typical absence seizures, and could be of pathological importance in patients with SSADH deficiency.     

Thermostimulation-Induced Modulation of Conditioned Reflex Movement-Related Reactions of Cortical Neurons of the Cat

In awake cats trained to perform a food-procuring conditioned operant reflex (placing movement), we studied impulse reactions of 86 neurons of the motor cortex (field 4) related to realization of the above movements. As conditioning stimuli (CS) initiating the reflex, we used either non-noxious electrocutaneous stimulation (ECS) of the contralateral forelimb or an acoustic stimulus (sound click). Impulsation of cortical neurons was recorded under conditions of (i) isolated presentation of the CS (control), (ii) presentation of the CS (either ECS or acoustic stimulus) combined with thermostimulation (heating with a miniature electric bulb) of the skin of the working forelimb, and (iii) the same, but with stimulation of the resting forelimb. When we recorded spike activity of neurons within the projection motor zone of the resting limb subjected to ESC, alternating thermostimulation of both forelimbs resulted in considerable intensification and an increase in the duration of neuronal responses, especially in cases where thermostimulation was applied to the working limb ipsilateral to the recording site (a two- to threefold increase). When spike reactions were recorded within the motor cortex of the working forelimb, thermostimulation resulted in a considerable increase in the intensity of these reactions and a decrease in their latency, but only when such stimulation was applied to the working forelimb. Thermostimulation of the resting (ipsilateral, subjected to ESC) limb evoked opposite effects (the intensity of neuronal reactions dropped). In both situations, placing movements remained within the control limits. When sound click was used as a distant CS, thermostimulation of the working limb enhanced neuronal responses, increased their duration by 50-100%, and also increased the time of forestalling of the movement initiation by spike neuronal reactions. Thermostimulation of the resting forelimb in this situation also suppressed neuronal reactions. We conclude that foreign stimulations directed toward modifications of the receptor model of the operant reflex experimental situation formed in the animal result in a decrease in the intensity of the spike responses of field-4 neurons and prolongation of the latencies of these responses, while stimulations promoting the inflow of afferent information to the cortical projection of the working limb evoke opposite effects, an increase in the intensity of neuronal spike responses and a decrease in their latencies.     

Dynamics of driven rhythm in neuronal assemblies in sensorimotor and visual cerebral cortices in rabbit

Coincident activity of pairs of neurons in the sensorimotor and visual areas of the cerebral cortex was studied in naive, learning, and trained rabbits during the formation of a hidden excitation focus in their central nervous system (a defensive dominanta) of the rhythmic nature. In the trained rabbits (as compared to the naive animals), percent of neuronal pairs (both neighboring and distant) in whose coincident activity the rhythm of stimulation prevailed was higher. In the visual cortex, percent of such pairs was significantly higher only for the distant neurons. Analysis of interaction between neurons in the visual and sensorimotor cortices revealed increasing the number of neuronal pairs with the driven rhythm while training. Such an increase was observed when both sensorimotor and visual neurons were considered as leading.     

Activation of spinally projecting and nitrergic neurons in the PVN following heat exposure

The present study investigated the effect of acute thermal stimulation in conscious rats on the production of Fos, a marker of increased neuronal activity, in spinally projecting and nitrergic neurons in the hypothalamic paraventricular nucleus (PVN). The PVN contains a high concentration of nitrergic neurons, as well as neurons that project to the intermediolateral cell column (IML) of the spinal cord that can directly influence sympathetic nerve activity (SNA). During thermal stimulation, the PVN is activated, but it is unknown whether spinally projecting PVN neurons and the nitrergic neurons are involved. Compared with controls, rats exposed to an environmental temperature of 39 degrees C for 1 h had a 10-fold increase in the number of cells producing Fos in the PVN (133 +/- 23 vs. 1,336 +/- 43, respectively, P < 0.0001). Of the spinally projecting neurons in the PVN of heated rats (98 +/- 10), over 20% expressed Fos. Additionally, of the nitrergic neurons (NADPH-diaphorase positive) located in the parvocellular PVN (723 +/- 17), 40% also expressed Fos (P < 0.0001 compared with controls). Finally, there was a significant increase in the number of spinally projecting neurons in the PVN that were nitrergic and expressed Fos after heat exposure (12%) compared with controls (0.1%) (P < 0.0001). These results suggest that spinally projecting and nitrergic neurons in the PVN may contribute to the central pathways activated by thermal stimulation.     

AT1 receptors in the nucleus tractus solitarii mediate the interaction between the baroreflex and the cardiac sympathetic afferent reflex in anesthetized rats

The cardiac "sympathetic afferent" reflex (CSAR) has been reported to increase sympathetic outflow and depress baroreflex function via a central angiotensin II (ANG II) mechanism. In the present study, we examined the role of ANG II type 1 (AT(1)) receptors in the nucleus tractus solitarii (NTS) in mediating the interaction between the CSAR and the baroreflex in anesthetized rats. We examined the effects of bilateral microinjection of AT(1) receptor antagonist losartan (100 pmol) into the NTS on baroreflex control of renal sympathetic nerve activity (RSNA) before and after CSAR activation by epicardial application of capsaicin (0.4 microg). Using single-unit extracellular recording, we further examined the effects of CSAR activation on the barosensitivity of barosensitive NTS neurons and the effects of intravenous losartan (2 mg/kg) on CSAR-induced changes in activity of NTS barosensitive neurons. Bilateral NTS microinjection of losartan significantly attenuated the increases in arterial pressure, heart rate, and RSNA evoked by capsaicin but also markedly (P < 0.01) reversed the CSAR-induced blunted baroreflex control of RSNA (Gain(max) from 1.65 +/- 0.10 to 2.22 +/- 0.11%/mmHg). In 17 of 24 (70.8%) NTS barosensitive neurons, CSAR activation significantly (P < 0.01) inhibited the baseline neuronal activity and attenuated the neuronal barosensitivity. In 11 NTS barosensitive neurons, intravenous losartan effectively (P < 0.01) normalized the decreased neuronal barosensitivity induced by CSAR activation. In conclusion, blockade of NTS AT(1) receptors improved the blunted baroreflex during CSAR activation, suggesting that the NTS plays an important role in processing the interaction between the baroreflex and the CSAR via an AT(1) receptor-dependent mechanism.     

A central role for the nitrate transporter NRT2.1 in the integrated morphological and physiological responses of the root system to nitrogen limitation in Arabidopsis

Up-regulation of the high-affinity transport system (HATS) for NO(3)(-) and stimulation of lateral root (LR) growth are two important adaptive responses of the root system to nitrogen limitation. Up-regulation of the NO(3)(-) HATS by nitrogen starvation is suppressed in the atnrt2.1-1 mutant of Arabidopsis (Arabidopsis thaliana), deleted for both NRT2.1 and NRT2.2 nitrate transporter genes. We then used this mutant to determine whether lack of HATS stimulation affected the response of the root system architecture (RSA) to low NO(3)(-) availability. In Wassilewskija (Ws) wild-type plants, transfer from high to low NO(3)(-) medium resulted in contrasting responses of RSA, depending on the level of nitrogen limitation. Moderate nitrogen limitation (transfer from 10 mm to 1 or 0.5 mm NO(3)(-)) mostly led to an increase in the number of visible laterals, while severe nitrogen stress (transfer from 10 mm to 0.1 or 0.05 mm NO(3)(-)) promoted mean LR length. The RSA response of the atnrt2.1-1 mutant to low NO(3)(-) was markedly different. After transfer from 10 to 0.5 mm NO(3)(-), the stimulated appearance of LRs was abolished in atnrt2.1-1 plants, whereas the increase in mean LR length was much more pronounced than in Ws. These modifications of RSA mimicked those of Ws plants subjected to severe nitrogen stress and could be fully explained by the lowered NO(3)(-) uptake measured in the mutant. This suggests that the uptake rate of NO(3)(-), rather than its external concentration, is the key factor triggering the observed changes in RSA. However, the mutation of NRT2.1 was also found to inhibit initiation of LR primordia in plants subjected to nitrogen limitation independently of the rate of NO(3)(-) uptake by the whole root system and even of the presence of added NO(3)(-) in the external medium. This indicates a direct stimulatory role for NRT2.1 in this particular step of LR development. Thus, it is concluded that NRT2.1 has a key dual function in coordinating root development with external NO(3)(-) availability, both indirectly through its role as a major NO(3)(-) uptake system that determines the nitrogen uptake-dependent RSA responses, and directly through a specific action on LR initiation under nitrogen-limited conditions.     

GABA-mediated synaptic inhibition of projection neurons in the antennal lobes of the sphinx moth,Manduca sexta

Responses of neurons in the antennal lobe (AL) of the moth Manduca sexta to stimulation of the ipsilateral antenna by odors consist of excitatory and inhibitory synaptic potentials. Stimulation of primary afferent fibers by electrical shock of the antennal nerve causes a characteristic IPSP-EPSP synaptic response in AL projection neurons. The IPSP in projection neurons reverses below the resting potential, is sensitive to changes in external and internal chloride concentration, and thus is apparently mediated by an increase in chloride conductance. The IPSP is reversibly blocked by 100 microM picrotoxin or bicuculline. Many AL neurons respond to application of GABA with a strong hyperpolarization and an inhibition of spontaneous spiking activity. GABA responses are associated with an increase in neuronal input conductance and a reversal potential below the resting potential. Application of GABA blocks inhibitory synaptic inputs and reduces or blocks excitatory inputs. EPSPs can be protected from depression by application of GABA. Muscimol, a GABA analog that mimics GABA responses at GABAA receptors but not at GABAB receptors in the vertebrate CNS, inhibits many AL neurons in the moth.     

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.     

Neuronal organization of the large-cell segment of the cat's red nucleus]

When studying the neuronal organization of the large-cell part of the red nucleus in cats by the Golgi and Golgi-Kopsch methods three types of neurons have been revealed: large (50-90 mu), medium-sized (20-50 mu) and small cells (8-20 mu). long axon and short-axon neurons were found as well as long-dendrite cells with few thorns (the length of the dendrites form 600-900 mu) and short-dendrite cells (up to 400 mu). On basis ofanalysis of neuronal groups found in the large-cell part of the red nucleus of the cat a neuronal map of this part of the central nervous sytem is composed.     

Dynamics of functional reciprocal connections between cerebral motor cortex neurons under stimulation in cats

Activity was recorded from neurons belonging to the representation of the forelimb in the motor cortex (sulcus cruciatus, L 7–9 mm) using multiple multi-channel/barrel electrodes during acute experiments on cats. Cross-correlation analysis of impulse trains was adopted to investigate dynamics of interneuronal connections during passive flexion and electrical stimulation of the limb contralateral to the recording site. It was found that neither passive bending nor electrical stimulation of the limb leads to a significant increase in the total number of direct relationships between cortical neurons. At the same time, passive flexion does produce a considerable decrease in the number of instances of both inputs operating in neighboring neurons (50–100 µm apart) and an increase in cells located further (between 100 and 400 µm) apart. Some increase in the number of direct inhibitory interactions between neighboring neurons was observed during electrical stimulation.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Nentskii Institute of Experimental Biology, Warsaw, Poland. Center of Experimental and Clinical Medicine, Warsaw, Poland. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 73–80, January–February, 1991.     

Correlations of neuronal spike discharges of VL neurons during spontaneous firing and during the activity evoked by peripheral stimulation

The temporal relations between simultaneously recorded neurons of the nucleus ventralis lateralis (VL) of cat thalamus were studied. The interaction and the functional connections between individual VL neurons are described. This was achieved with an application of cross correlation techniques. The response patterns of different individual neurons to somatic sensory and photic stimuli were also analyzed. For the purpose of classifying neurons as thalamocortical relay cells (T-C) and non relay cells (N-C) which do not project to the motor sensory cortex antidromic cortical stimulation was used. This stimulation was also used as conditioning one when proceeded peripheral stimuli. To analyze the nonspecific specific interactions upon single neurons conditioning photic stimuli were applied. The results show that T-C neurons are antidromically excited from a wide cortical areas and that the functional interaction between T-C neurons is mediated by a shared input from common sources. It is further postulated that N-C cells interposed between relay neurons subserve the functions of gating units modifying the neuronal network of lateral ventral nucleus of the thalamus.     

Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1

Several processes by which astrocytes protect neurons during ischemia are now well established. However, less is known about how neurons themselves may influence these processes. Neurons release zinc (Zn2+) from presynaptic terminals during ischemia, seizure, head trauma, and hypoglycemia, and modulate postsynaptic neuronal function. Peak extracellular zinc may reach concentrations as high as 400 microM. Excessive levels of free, ionic zinc can initiate DNA damage and the subsequent activation of poly(ADP-ribose) polymerase 1 (PARP-1), which in turn lead to NAD+ and ATP depletion when DNA damage is extensive. In this study, cultured cortical astrocytes were used to explore the effects of zinc on astrocyte glutamate uptake, an energy-dependent process that is critical for neuron survival. Astrocytes incubated with 100 or 400 microM of zinc for 30 min showed significant decreases in ATP levels and glutamate uptake capacity. These changes were prevented by the PARP inhibitors benzamide or DPQ (3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone) or PARP-1 gene deletion (PARP-1 KO). These findings suggest that release of Zn2+ from neurons during brain insults could induce PARP-1 activation in astrocytes, leading to impaired glutamate uptake and exacerbation of neuronal injury.     

Presynaptic inhibition of excitatory input from the substantia nigra to caudate nucleus neurons by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392)

The effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl) propoxy]-2(1H)-quinolinone (OPC-4392) on neuronal activities of the caudate nucleus (CN) were investigated in cats anesthetized with alpha-chloralose using a microiontophoretic method. In the CN neurons of which spikes elicited by stimulation of the pars compacta of substantia nigra (SN) were suppressed by iontophoretically applied domperidone, a dopamine D-2 receptor antagonist, application of OPC-4392 (100-200 nA) inhibited the spike generation induced by SN stimulation. Conversely, the CN neurons insensitive to domperidone were unaffected by OPC-4392. Iontophoretic application of CPC-4392 up to 200 nA did not affect glutamate-induced firing of the CN neurons, of which the firing was blocked by dopamine less than 100 nA. In addition, OPC-4392 did not inhibit firing induced by bromocriptine, a dopamine D-2 agonist; while domperidone suppressed the bromocriptine-induced firing without affecting the glutamate-induced firing. These results suggest that OPC-4392 acts on the dopaminergic nerve terminals and inhibits excitatory transmission from the SN to the CN.     

Effect of desglycine-arginine vasopressin on the excitability of the command neurons of the defensive reflex in the edible snail

Perfusion of the snail (Helix lucorum L.) CNS with DG-AVP (concentration 10(-6) M) in the course of low frequency intracellular stimulation (2-4-minute interval) of the defensive reflex command neurons led to an increase in the excitability. It was expressed both in the reduction of the spike generation latency, in the increased number of spikes in response to fixed stimuli, and in the activation of pacemaker potentials. If DG-AVP was added to the medium during endoneuronal habituation, there was no increase in the excitability. It is supposed that modification of the neuronal excitability may be caused by the DG-AVP effect on the pacemaker mechanism.