Modelling corticothalamic feedback and the gating of the thalamus by the cerebral cortex

Morphological studies have shown that excitatory synapses from the cortex constitute the major source of synapses in the thalamus. However, the effect of these corticothalamic synapses on the function of the thalamus is not well understood because thalamic neurones have complex intrinsic firing properties and interact through multiple types of synaptic receptors. Here we investigate these complex interactions using computational models. We show first, using models of reconstructed thalamic relay neurones, that the effect of corticothalamic synapses on relay cells can be similar to that of afferent synapses, in amplitude, kinetics and timing, although these synapses are located in different regions of the dendrites. This suggests that cortical EPSPs may complement (or predict) the afferent information. Second, using models of reconstructed thalamic reticular neurones, we show that high densities of the low-threshold Ca2+ current in dendrites can give these cells an exquisite sensitivity to cortical EPSPs, but only if their dendrites are hyperpolarized. This property has consequences at the level of thalamic circuits, where corticothalamic EPSPs evoke bursts in reticular neurones and recruit relay cells predominantly through feedforward inhibition. On the other hand, with depolarized dendrites, thalamic reticular neurones do not generate bursts and the cortical influence on relay cells is mostly excitatory. Models therefore suggest that the cortical influence can either promote or antagonize the relay of information, depending on the state of the dendrites of reticular neurones. The control of these dendrites may therefore be a determinant of attentional mechanisms. We also review the effect of corticothalamic feedback at the network level, and show how the cortical control over the thalamus is essential in co-ordinating widespread, coherent oscillations. We suggest mechanisms by which different modes of corticothalamic interaction would allow oscillations of very different spatiotemporal coherence to coexist in the thalamocortical system.     

Effect of serotonin on the activity of the neurons involved in the realization of the avoidance reflex of the snail

Bath application of 10(-5) mol/l of serotonin (5-HT) elicited a 50% increase of summary EPSPs recorded in command neurones for avoidance behaviour. No significant changes of rest potential and input resistance were seen in these cells. 5-HT evoked an increase of spontaneous level of firing in motoneurones involved in the same reflex, as well as an increase in the number of spikes which paralleled increase of EPSPs to the same stimulus in command neurones. In sensory cells, presynaptic to the command neurones, application of 5-HT evoked a significant increase of excitability and of input resistance. Monosynaptic EPSPs recorded in the command neurones showed a 40% increase after serotonin application. It is concluded that the major locus of plastic changes evoked by 5-HT application in the neuronal chain underlying avoidance reflex is the synaptic contact between sensory and command neurones.     

Effect of thyroliberin on membrane potential and pattern of spontaneous activity of neurons of the respiratory center in rats in vitro

On frontal brainstem slices of rat by means of whole-clamp recordings, we investigated effects of TRH (10(-8) [symbol: see text]) on membrane potential and firing pattern of the neurones in ventrolateral area of the solitary tract nucleus and pre-Botzinger complex. TRH induced a membrane depolarisation and an increase in spontaneous activity of the respiratory centre neurones. After TRH administration, a shortening of time intervals between the beginning of bursts was found in bursting neurones of the pre-Botzinger complex. In some silent neurones, TRH elicited appearance of firing activity, so the silent neurones of the solitary tract nucleus were transformed into tonic while the silent pre-Botzinger complex neurones were transformed into bursting ones. Thus, there is a direct regulatory effect of TRH on the respiratory centre neurones at the level of their membrane.     

Cholinergic transmission at mechanosensory afferents in the crayfish terminal abdominal ganglion

Electrical stimulation of mechanosensory afferents innervating hairs on the surface of the exopodite in crayfish Procambarus clarkii (Girard) elicited reciprocal activation of the antagonistic set of uropod motor neurones. The closer motor neurones were excited while the opener motor neurones were inhibited. This reciprocal pattern of activity in the uropod motor neurones was also produced by bath application of acetylcholine (ACh) and the cholinergic agonist, carbamylcholine (carbachol). The closing pattern of activity in the uropod motor neurones produced by sensory stimulation was completely eliminated by bath application of the ACh blocker, d-tubocurarine, though the spontaneous activity of the motor neurones was not affected significantly. Bath application of the acetylcholinesterase inhibitor, neostigmine, increased the amplitude and extended the time course of excitatory postsynaptic potentials (EPSPs) of ascending interneurones elicited by sensory stimulation. These results strongly suggest that synaptic transmission from mechanosensory afferents innervating hairs on the surface of the tailfan is cholinergic.Bath application of the cholinergic antagonists, dtubocurarine (vertebrate nicotinic antagonist) and atropine (muscarinic antagonist) reversibly reduced the amplitude of EPSPs in many identified ascending and spiking local interneurones during sensory stimulation. Bath application of the cholinergic agonists, nicotine (nicotinic agonist) and oxotremorine (muscarinic agonist) also reduced EPSP amplitude. Nicotine caused a rapid depolarization of membrane potential with, in some cases, spikes in the interneurones. In the presence of nicotine, interneurones showed almost no response to the sensory stimulation, probably owing to desensitization of postsynaptic receptors. On the other hand, no remarkable changes in membrane potential of interneurones were observed after oxotremorine application. These results suggest that ACh released from the mechanosensory afferents depolarizes interneurones by acting on receptors similar to vertebrate nicotinic receptors.Abbreviations ACh cetylcholine - mns motor neurones - asc int ascending interneurone     

Pre & postsynaptic tuning of action potential timing by spontaneous GABAergic activity

Frequency and timing of action potential discharge are key elements for coding and transfer of information between neurons. The nature and location of the synaptic contacts, the biophysical parameters of the receptor-operated channels and their kinetics of activation are major determinants of the firing behaviour of each individual neuron. Ultimately the intrinsic excitability of each neuron determines the input-output function. Here we evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a simple computational model that reproduce subthreshold membrane properties. Besides the well-documented control of neuronal excitability, spontaneous background GABAergic activity has a major detrimental effect on spike timing. In fact, GABA(A) receptors tune the relationship between the excitability and fidelity of pyramidal neurons via a postsynaptic (the reversal potential for GABA(A) activity) and a presynaptic (the frequency of spontaneous activity) mechanism. GABAergic activity can decrease or increase the excitability of pyramidal neurones, depending on the difference between the reversal potential for GABA(A) receptors and the threshold for action potential. In contrast, spike time jitter can only be increased proportionally to the difference between these two membrane potentials. Changes in excitability by background GABAergic activity can therefore only be associated with deterioration of the reliability of spike timing.     

The role of GABA-ergic regulation in organizing spontaneous and evoked activity of the septal neurons

Effects of GABA, pentobarbital and picrotoxin upon spontaneous and evoked activity of neurones of the medial septal nucleus and the nucleus of the diagonal band (MS-DB) were investigated in the guinea pig septal slices. GABA and pentobarbital have similar effect upon all neurones, but the cells with a regular single spike and rhythmic burst activity of pacemaker type were less sensitive to their inhibitory influence. Picrotoxin affects neither frequency, nor pattern of activity. Electrical stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the neurones (74%); the remaining cells reacted mainly with an initial burst. GABA and pentobarbital increased the duration of the initial inhibition and revealed it in all cells with initial excitation in the control state. Picrotoxin did not influence this type of response, but revealed initial short-latency bursts in the cells with inhibitory effect in control state. The experiments show double nature of the effect of afferent stimulation controlling the activity of the MS-DB neurones. The mechanism of synchronization of the rhythmic activity in MS-DB, resulting in generation of the hippocampal theta-rhythm, is discussed.     

Differential effects of prostaglandin F2 alpha on oxytocinergic and non-oxytocinergic neurones in the paraventricular nucleus of the lactating rat

The effects of the prostaglandin F2 alpha (PGF2 alpha) given into the third cerebral ventricle on the unit activity of neurosecretory neurones in the paraventricular nucleus (PVN) were studied in urethane-anesthetized rats. The firing activity of PVN neurones was recorded extracellularly and 50 neurones were antidromically identified as neurosecretory neurones. Thirty of them were classified oxytocinergic neurones because they gave a burst of action potential 12-15 sec before reflex milk ejection and the remaining twenty PVN neurones which showed no response prior to reflex milk ejections were regarded as non-oxytocinergic ones. Twenty-five (83%) of the30 oxytocinergic neurones increased in the firing rate following the intraventricular (IVT) injection of PGF2 alpha (500ng in 1 microliter of isotonic saline) and the responses lasted for about 20-30 min. The remaining 5 (17%) oxytocinergic neurones showed no response in the firing rate to IVT PGF2 alpha. Fifteen (75%) of the 20 nonoxytocinergic neurones decreased in the firing activity in response to IVT PGF2 alpha, and the remaining 5 (25%) of them showed no response. IVT injection of isotonic saline (1 microliter) did not affect the firing activity of both the oxytocinergic and nonoxytocinergic cells. The intramammary pressure was slightly increased by the IVT administration of PGF2 alpha. These findings indicate that IVT PGF2 alpha has a differential action on oxytocinergic and non-oxytocinergic neurones in rats.     

Postsynaptic potentials in the myocardium of snails in the genus Helix

Cardioregulating neurones in the right parietal and visceral ganglia of the snail evoke postsynaptic potentials of various duration, amplitude and polarity in the auricular and ventricular myocardium. Inhibitory neurones with a marked background activity (1-2 imp/s) evoke IPSPs with a duration of 150-200 msec and a latent period of 160-220 msec in the auricle, these potentials being blocked by tubocurarine. EPSPs of approximately the same duration may be recorded in the ventricle during stimulation of the commanding neurones of the pneumostome LPa3 and PPa/3, as well as unidentified neurones. Action potentials in some other identified cardiostimulating neurones (PPa7, V1, V6) induce slow and sustained depolarization in the myocardium. Functional specificity of elements within fast and slow regulatory systems is suggested: discrete IPSPs and EPSPs account mainly for coordination of the systolic contractions of the auricle and ventricle, whereas long-lasting PSPs affect the frequency and intensity of the whole heart.     

Pattern and correlation of fast and slow spontaneous unit activity in the visual cortex

Spontaneous unit activity in the visual cortex and its changes during stimulation by continuous light or flashes were investigated in waking rabbits. The study of distributions of adjacent intervals showed that the neurons differ in the ratio of burst (fast, with intervals of up to 15–40 msec) and nonburst (slow) activity and in the character of changes from one type of activity to the other. Of the total number of spikes 63% were outside bursts; the ratio of their number to the number of spikes within bursts consisting of two or of three or more spikes was 27:3:1. The relative stability of the burst structure of spontaneous activity and the limited number of spikes in them (on average 2.4) were demonstrated. Bursts of three or more spikes (mean 3.6) were irregular, and in 79% of them a longer interval (18.6±2.4 msec) was observed before the shortest interval (7.9±0.9 msec). Bursts of spikes of most neurons during photic stimulation contain more spikes with shorter intervals; they also began more frequently with the shortest interval, possibly signifying an increase in the steepness and amplitude of the EPSPs lying at their basis. However, in 20% of neurons spontaneous bursts included more spikes and with shorter intervals than bursts evoked by flash stimulation.Research Institute of Psychiatry, Ministry of Health of the RSFSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 311–320, July–August, 1979.     

Ca2+-dependent depolarization and burst firing of rat CA1 pyramidal neurones induced by N-methyl-D-aspartic acid and quinolinic acid: antagonism by 2-amino-5-phosphonovaleric and kynurenic acids

The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (NMDA), and quinolinic (QUIN) acids were investigated using intracellular recording from CAl pyramidal neurones in slices of rat hippocampus. QUIS evoked only simple action potentials superimposed upon a depolarization which attained a clear plateau. When this level had been reached, increased ejecting currents did not produce further depolarization. By contrast, with low currents NMDA and QUIN elicited small membrane depolarizations which triggered bursts of action potentials superimposed upon rhythmically occurring depolarizing shifts. Larger currents caused depolarization which if sufficiently large completely blocked spike activity. Tetrodotoxin (TTX) prevented the spikes evoked by QUIS and the bursts of action potentials seen with NMDA and QUIN, and the rhythmic depolarizing shifts then appeared as broad spikes of up to 50 mV in amplitude. These and the underlying membrane depolarization were blocked by Co2+, by the NMDA antagonist D(-)-2-amino-5-phosphonovaleric acid (DAPV), and by kynurenic acid (KYNU). It thus appears that the depolarization and burst firing of rat CAl pyramidal neurones elicited by NMDA and QUIN are Ca2+ dependent while the actions of QUIS are not.     

Effects of transections and electrical coagulations in the medulla oblongata upon the activities in the respiratory muscles of the crucian carp (author's transl)]

The following conclusions may be drawn from the results in this work. The respiratory cycles are formed by the neuronal machinery in the reticular formation under the posterior part of the vagal motor nucleus. The motor neurones or the neuronal networks composing the motor nucleus of the respiratory muscles tonically discharge the action potentials, when the neurones or the networks are released from the inhibitory influences of the interneurones connecting the neuronal machinery to the motor neurones. Furthermore, the interneurones probably generate the tonic discharges after removing the inhibitory influences of the other interneurones or the neuronal machinery on them. A reflex mouth closing is elicited by a mechanical stimulus applying on the upper lip. The motor neurones of the m. adductor mandibulae are activated via only one synapse in the reflex. The reflex action potentials recorded from the motor nerve reduce in amplitude at the resting phase of the nerve in the respiratory cycles. These results suggest that the respiratory motor neurones are by nature spontaneous generators of the tonic action potentials and, in the time of the normal breathing, the tonic activity is interrupted by an inhibitory influence of the neuronal machinery generating the respiratory cycles.     

Agonistic and antagonistic activity of glutamate analogs on neuromuscular excitation in the walking limbs of lobsters.

Forty-six analogs of L-glutamate were tested for activity on muscle fibers in the walking limbs of lobsters. Effects on the membrane potential, input resistance, and amplitude of neurally evoked EPSPs and IPSPs were studied as well as effects on applied L-glutamate. Seventeen of the compounds studied depolarized the muscle fibers in a manner indicative of an agonistic action on receptors in the neuromuscular excitatory membrane. Six analogs selectively reduced the amplitude of evoked EPSPs, and at least three of these (kainic acid, D-glutamate, and D-aspartate) antagonized the excitatory action of applied L-glutamate. Kainic acid was the most potent of the blockers of neuromuscular excitation, but even it was relatively weak since a concentration of 1 mM was required for an apparent effect. Generally those analogs in the L-configuration which possessed activity, had agonistic actions, whereas those in the D-configuration were usually antagonistic. These observations provide pharmacological evidence for the concept that L-glutamate is the transmitter agent which mediates neuromuscular excitation in the walking limbs of lobsters. In addition, our results are consistent with recent studies which indicate that L-aspartate may also function in this neuromuscular excitatory process.     

Electrophysiological properties of the isolated vestibulocerebellar complex of the frog in vitro

Parameters of the electrical activity of the isolated vestibulocerebellar complex of the frog were studied under in vitro conditions. In the region of the vestibular nucleus (nc. VIII), in the presence of stimulation of the stato-acoustic nerve (n. VIII), responses from efferent vestibular neurones and from unidentified (probably vestibulospinal) neurones were recorded. The latent periods of their excitatory postsynaptic potentials (EPSPs, 1.4-2.2 ms) were indicative of mono- and disynaptic connection. Inhibitory postsynaptic potentials (IPSPs) were also observed. Stimulation of the auricular lobe of the cerebellum evoked monosynaptic IPSPs, an EPSP-IPSP complex or pure EPSPs in nc. VIII, the latter probably by way of collaterals to the cerebellum. The inhibitory character of the effect of efferents from the cerebellum to the neurones of nc. VIII was demonstrated in the focal synaptic potential and in spontaneous and evoked unit activity. If n. VIII was stimulated, both focal and unit extra- and intracellular responses characteristic of activation of the Purkinje cells by mossy (MF) or climbing (CF) afferent fibres were recorded in the cerebellar cortex. The electrophysiological picture indicates that both synaptic transmission and the functional manifestations of the individual neurones are preserved in the tested preparation.     

Agonistic and antagonistic activity of glutamate analogs on neuromuscular excitation in the walking limbs of lobsters

Forty-six analogs of L -glutamate were tested for activity on muscle fibers in the walking limbs of lobsters. Effects on the membrane potential, input resistance, and amplitude of neurally evoked EPSPs and IPSPs were studied as well as effects on applied L -glutamate. Seventeen of the compounds studied depolarized the muscle fibers in a manner indicative of an agonistic action on receptors in the neuromuscular excitatory membrane. Six analogs selectively reduced the amplitude of evoked EPSPs, and at least three of these (kainic acid, D -glutamate, and D -aspartate) antagonized the excitatory action of applied L -glutamate. Kainic acid was the most potent of the blockers of neuromuscular excitation, but even it was relatively weak since a concentration of 1 mM was required for an apparent effect. Generally those analogs in the l-configuration which possessed activity, had agonistic actions, whereas those in the d-configuration were usually antagonistic. These observations provide pharmacological evidence for the concept that L -glutamate is the transmitter agent which mediates neuromuscular excitation in the walking limbs of lobsters. In addition, our results are consistent with recent studies which indicate that l-aspartate may also function in this neuromuscular excitatory process.     

The Intrinsic Electrophysiological Characteristics of Fly Lobula Plate Tangential Cells: III. Visual Response Properties

In this last paper in a series (Borst and Haag, 1996; Haag et al., 1997) about the lobula plate tangential cells of the fly visual system (CH, HS, and VS cells), the visual response properties were examined using intracellular recordings and computer simulations. In response to visual motion stimuli, all cells responded mainly by a graded shift of their axonal membrane potential. While ipsilateral motion resulted in a graded membrane potential shift, contralateral motion led to distinct EPSPs. For HS cells, simultaneous extracellular recorded action potentials of a spiking interneuron, presumably the H2 cell, corresponded to the EPSPs in the HS cell in a one-to-one fashion. When HS cells were hyperpolarized during ipsilateral motion, they mainly produced action potentials, but when they were hyperpolarized during contralateral motion only a slight increase of EPSP amplitude, could be observed. Intracellular application of the sodium channel blocker QX 314 abolished action potentials of HS cells while having little effect on the graded membrane response to ipsilateral motion. HS and CH cells were also studied with respect to their spatial integration properties. For both cell types, their graded membrane response was found to increase less than linearly with the size of the ipsilateral motion pattern. However, while for HS cells various amounts of hyperpolarizing current injected during motion stimulation led to different saturation levels, this was not the case for CH cells. In response to a sinusoidal velocity modulation, CH cells followed pattern motion only up to 10 Hz modulation frequency, but HS cells still revealed significant membrane depolarizations up to about 40 Hz.In the computer simulations, the compartmental models of tangential cells, as derived in the previous papers, were linked to an array of local motion detectors. The model cells revealed the same basic response features as their natural counterparts. They showed a response saturation as a function of stimulus size. In CH-models, however, the saturation was less pronounced than in real CH-cells, indicating spatially nonuniform membrane resistances with higher values in the dendrite. As in the experiments, HS models responded to high-frequency velocity modulation with a higher amplitude than did CH models.     

Modulation of electrical activity of neuron RPa2 ofHelix pomatia

Neuron RPa2 ofHelix pomatia can generate rhythmic (beating) or periodic (bursting) activity. A spontaneous switch from beating to bursting activity takes place in the course of tens of minutes. Similar changes in electrical activity can be induced by the addition of the water-soluble fraction obtained from a homogenate of snail ganglia to the experimental chamber. Artificial polarization of the membrane of neuron RPa2 by asteady inward current leads to an increase in the duration of intervals between bursts and to a decrease in the number of action potentials in the burst. With an increase in amplitude of the polarizing current, action potential generation ceases completely, but generation of waves of membrane potential persists. If the voltage on the neuron membrane is clamped, periodic fluctuations of membrane current disappear. It is suggested that action potential generation by neurons RPa2 is determined by the properties of the potential-dependent conductance of its membrane, i.e., that it is endogenous in origin and can be regulated by compounds acting on the membrane. These compounds, secreted by other neurons, resemble neurotransmitters or neurohormones.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 4, pp. 406–412, July–August, 1981.     

Relation between fast and slow elemental synaptic potentials in command neurons in Helix lucorum taurica L

In experiments on a semi-intact snail preparation and a preparation of the snail isolated CNS, after spikes (Sp) evoked in presynaptic neurones by depolarizing current, not only rapid (R) EPSPs emerged in the command neurones of the defensive reaction of closing the pneumostome, but they were also followed by slow (S) EPSPs lasting over 2 min. For each single synaptic contact, the R and S EPSP amplitudes were in a good linear correspondence. In different synapses no direct connection was observed between R EPSP and S EPSP. It is suggested that R and S EPSPs may set in as a result of the action of different substances on the command neurones. Functional significance of S EPSPs with different amplitudes in different command neurones may consist in a prolonged specific preparation of the neurones for the action of stimuli.     

Parallel processing of mechanosensory inputs from the locust ovipositor by intersegmental and local interneurones

The neural pathways underlying the processing of signals from locust (Schistocerca gregaria) ovipositor hairs by different classes of interneurones are investigated.Spikes in the sensory neurones from these hairs evoke chemically-mediated, unitary EPSPs with a short and constant latency in six identified non-giant projection interneurones with cell bodies in the terminal abdominal ganglion. Five of these interneurones receive direct inputs from the valves ipsilateral to their neuropilar branches, whereas the other receives direct inputs from valves on both sides. The sensory neurone from a single hair makes divergent connections with several interneurones and those from different hairs make convergent connections with a given interneurone. The amplitude of the EPSPs evoked depends on the position of a hair along the proximal-distal axis of the valve, with sensory neurones from more distal hairs generating larger amplitude EPSPs.Deflection of hairs also excites three of the four giant projection interneurones through polysynaptic pathways and some local interneurones in the terminal abdominal ganglion through monosynaptic connections. Branches of non-giant projection interneurones, local interneurones, but not those of the giant interneurones, overlap the axon terminals of the ovipositor hair afferents in the terminal abdominal ganglion.     

The excitability of neurons of the medial septal area in brain slices from hibernating and active Citellus undulatus susliks]

Spontaneous and evoked neuronal activity of the medical septum-diagonal band complex (MS-DB) has been investigated in slices from the brain of hibernating and active ground squirrels, as well as guinea pigs. In all experimental groups, the majority of the MS-DB neurones exhibited high regular of rhythmic burst spontaneous activity which persisted even after synaptic blockade in half of the neuronal population. Under the same conditions, the activity of the surrounding structures was completely suppressed. The density of the spontaneously active neurones in the slices, as well as the mean frequency of discharges in the MS-DB of hibernating ground squirrels, were significantly higher than in active ground squirrels and guinea pigs. Stimulation of the medial forebrain bundle evoked initial suppression of the activity in the majority of MS-DB units; in many of them, the suppression was followed by a burst discharge. Neurones with background rhythmic burst activity always reacted by resetting the spontaneous bursts. In total, 50-60% of the MS-DB neurones in active ground squirrels and guinea pigs reacted by post-inhibitory bursts, whereas in hibernating animals these responses were observed nearly in all neurones. Threshold values of the stimulating current were lower in hibernating animals; the intraburst density of spikes was increased.     

Effects of changes in K+ in the perilymphatic fluid on the activity of vestibular receptors in the frog

The effect of rapid changes in K+ concentration (from 0 up to 5 mM) in the perilymphatic fluid was tested on ampullar receptor activity in isolated semicircular canals of the frog. The effects of the different K-concentrations were evaluated by recording both the transepithelium potentials (Adc) and the postsynaptic potentials (EPSPs and spikes discharge) led off from the ampullar nerve. The results have clearly demonstrated that crista ampullaris sensory cells are extremely sensitive to K-changes (+/- 0.25 mM). In fact both transepithelial potentials and discharge activity (EPSPs and propagated spikes) of first order vestibular neurones may be decreased or increased by decreasing or increasing the K-concentration in the outer fluid. The possible mechanism of action of K+ on ampullar receptors is discussed.