Polysynaptic Responses Research Articles

Modulation of synaptic plasticity in the hippocampus and piriform cortex by physiologically meaningful olfactory cues in an olfactory association task

Animals were trained to discriminate two natural odors while another group was trained to discriminate between a patterned electrical stimulation distributed on the lateral olfactory tract (LOT), labelled olfaco-mimetic stimulation (OMS), used as an olfactory cue versus a natural odor. No statistically significant difference was observed in behavioral data between these two groups. The animals trained to learn the meaning of the OMS exhibited a gradual long-term potentiation (LTP) phenomenon in the piriform cortex. When a group of naive animals was pseudo-conditioned, giving the OMS for the same number of sessions but without any olfactory training, no LTP was recorded. These results indicate that the process of learning olfactory association gradually potentiates cortical synapses in a defined cortical terminal field, and may explain why LTP in the piriform cortex is not elicited by the patterned stimulation itself, but only in an associative context. As olfactory and hippocampus regions are connected via the lateral entorhinal cortex, the olfactomimetic model was used to study the dynamic of involvement of the dentate gyrus (DG) in learning and memory of this associative olfactory task. Polysynaptic field potentials, evoked by the LOT stimulation, were recorded in the molecular layer of the ipsilateral DG. An early and rapid (2nd session) potentiation was observed when a significant discrimination of the two cues began to be observed. The onset latency of the potentiated response was 30–40 ms. When a group of naive animals was pseudoconditioned, no change was observed. Taken together, these results support the hypothesis that early activation of the DG during the learning of olfactory cue allows the progressive storage of olfactory information in a defined set of potentiated cortical synapses. The onset latency of the polysynaptic potentiated responses suggests the existence of a reactivating hippocampal loops during the processing of olfactory information.

Contribution of single-unit spike waveform changes to temperature-induced alterations in hippocampal population spikes.

Brain temperature changes accompany exploratory behavior and profoundly affect field potential amplitudes recorded in hippocampus. The waveform alterations in fascia dentata include a reduction in population spike area, which might be explained by fewer granule cells firing in response to a given stimulus or by an alteration in the size or shape of the individual action potentials. This study was designed to assess these alternate possibilities. In experiment 1, changes in the shape and firing rates of single cells recorded in the fascia dentata of awake rats were compared with changes in the population spike before and after a bout of activity. Single-unit amplitudes were significantly reduced following exploration, and there was a small (< 3%) change in unit spike-width. These changes, however, were insufficient to account, in a linear fashion, for the entire decline in the population spike. In experiment 2, radiant heat was used to manipulate brain temperature in anesthetized rats. As in the first experiment, the magnitude of change in the extracellular units was much smaller than the change in population spike amplitude. The spontaneous firing rates of the cells were also modified by brain temperature changes. In experiment 3, the polysynaptic, contralateral commissural response (which covaries with changes in the ipsilateral population spike at a fixed temperature) was measured as a function of either exploratory behavior or radiant heat. The relationship between the ipsilateral population spike and corresponding polysynaptic commissural response was altered following exploration and passive warming in a manner consistent with a reduction in net granule cell output, reduced transmission efficacy through the polysynaptic circuit, or a combination of these. Taken together these data suggest that at least two factors contribute to temperature-dependent changes in the perforant path-evoked population spikes recorded in the fascia dentata: changes in the size of individual action potentials and alterations in discharge of action potentials in response to a given stimulus.

Modulation of electrically elicited blink reflex components by visual and acoustic prestimuli in man

The effects of a prestimulus on the electrically elicited blink reflex components were investigated in 20 healthy subjects. In the first group of 10 subjects (warned group), electric shocks were delivered in isolation or preceded, at an interstimulus interval (ISI) of 0.1 s, 1 s, or 10 s, by a visual or acoustic warning stimulus. In the second group of 10 subjects (unwarned group), the electric shocks were delivered either in isolation or preceded, at the same ISI, by visual or acoustic stimuli having no warning value. The modulation of the three blink reflex components was then analysed. Compared to the baseline condition, the R1 oligosynaptic component was enhanced at 0.1 s and 1 s ISI, in the warned group with the visual prestimulus, but only at 0.1 s after a visual and acoustic prestimulus in the unwarned group. On the contrary, the polysynaptic responses showed a different course: R2 was significantly reduced at the 0.1 s interval in the warned group with both the prestimuli, and only with the visual prestimulus in the unwarned group. The R3 was inhibited at all three intervals with the visual prestimulus, and at the 0.1 s and 1 s with the acoustic one in the warned group, and only at 0.1 s in the unwarned group, both after visual and acoustic prestimuli. The decrement in R2 and R3 observed with the shortest interval was probably related to the prepulse inhibition of startle reflex. Furthermore, only R3 was still inhibited at longer intervals, when the sustained processes of attention may have influenced this component. Perhaps this combination of events represents, in the warned group, the best preparation for voluntary reflex reaction.

A stable late soleus EMG response elicited by cortical stimulation during voluntary ankle dorsiflexion

Transcranial electrical or magnetic stimulation was performed in 47 experiments on 42 normal adult subjects. Surface compound muscle action potentials were recorded from the antagonistic tibialis anterior (TA) and soleus (SOL) muscles. A stable late response recorded from SOL during voluntary ankle dorsiflexion is described and called soleus MEP-80. Its origin has been studied with different experimental procedures. 1. It is only obtained during active voluntary dorsiflexion of the ankle within 70–100 msec (mean 86.9 ± 6.4 msec) whereas passive dorsiflexion does not promote such a response. The size of SOL MEP-80 was always bigger than the primary SOL response. 2. A similar constant response has not been obtained during voluntary plantar flexion from SOL and TA muscles. 3. SOL MEP-80 is not changed significantly by the Jendrassik manoeuvre. 4. It is not obtained or is suppressed when the subject is sitting with the feet free in space. On the other hand, it is obtained when the subject is standing, especially when standing is made difficult. 5. SOL MEP-80 has not been obtained by brain-stem, spinal cord or root stimulation. 6. A later response of longer than 100 msec latency was sometimes obtained at rest but such an S100 soleus response was abolished or transformed to the SOL MEP-80 immediately during ankle dorsiflexion. 7. It is concluded that SOL MEP-80 is a polysynaptic extensor response related to postural mechanisms and originating through convergence of descending motor commands and peripheral sensory feedback.

A stable late soleus EMG response elicited by cortical stimulation during voluntary ankle dorsiflexion.

Transcranial electrical or magnetic stimulation was performed in 47 experiments on 42 normal adult subjects. Surface compound muscle action potentials were recorded from the antagonistic tibialis anterior (TA) and soleus (SOL) muscles. A stable late response recorded from SOL during voluntary ankle dorsiflexion is described and called soleus MEP-80. Its origin has been studied with different experimental procedures. (1) It is only obtained during active voluntary dorsiflexion of the ankle within 70-100 msec (mean 86.9 +/- 6.4 msec) whereas passive dorsiflexion does not promote such a response. The size of SOL MEP-80 was always bigger than the primary SOL response. (2) A similar constant response has not been obtained during voluntary plantar flexion from SOL and TA muscles. (3) SOL MEP-80 is not changed significantly by the Jendrassik manoeuvre. (4) It is not obtained or is suppressed when the subject is sitting with the feet free in space. On the other hand, it is obtained when the subject is standing, especially when standing is made difficult. (5) SOL MEP-80 has not been obtained by brain-stem, spinal cord or root stimulation. (6) A later response of longer than 100 msec latency was sometimes obtained at rest but such an S100 soleus response was abolished or transformed to the SOL MEP-80 immediately during ankle dorsiflexion. (7) It is concluded that SOL MEP-80 is a polysynaptic extensor response related to postural mechanisms and originating through convergence of descending motor commands and peripheral sensory feedback.

Pentylenetetrazol causes polysynaptic responses to appear in the dentate gyrus.

In a particular brain region specific changes in inhibition or excitation may be the basis of seizure initiation. Alternatively, changes in the balance of excitation and inhibition in the circuit, which may be detectable as polysynaptic responses may be more important indicators of epileptogenesis. That the appearance of polysynaptic responses precedes the initiation and, therefore, may be necessary for the onset of epileptiform activity in the hippocampal-parahippocampal circuit was tested using the chemical convulsant pentylenetetrazol. Excitation and paired-pulse inhibition were measured in CA1 and the dentate gyrus of the urethane-anaesthetized rat before and after administration of pentylenetetrazol. In addition, three polysynaptic responses were monitored. In both CA1 and the dentate gyrus, pentylenetetrazol, 100 mg/kg, caused a trend towards increased excitability and caused a relatively mild loss of inhibition. Two polysynaptic responses appeared in the dentate gyrus after the administration of pentylenetratrazol, both apparently mediated through the entorhinal cortex. A polysynaptic response of the CA1 pyramidal neurons to contralateral angular bundle stimulation was not observed. These experiments demonstrate that pentylenetetrazol will facilitate only the appearance of polysynaptic responses mediated through the entorhinal cortex. These results support the hypothesis that pentylenetetrazol has a specific action within the entorhinal cortex that may facilitate the synchronization and spread of epileptiform activity. These results are also consistent with the hypothesis that the appearance of polysynaptic responses may be necessary for the onset of epileptogenesis in the hippocampal-parahippocampal circuit.

Plantar F-P complex (F wave and polysynaptic responses) monitoring for spinal cord ischemia in aortic surgery

Plantar F-P complex (F wave and polysynaptic responses) monitoring for spinal cord ischemia in aortic surgery

Neurophysiological changes of spiny neurons in rat neostriatum after transient forebrain ischemia: an in vivo intracellular recording and staining study.

The spontaneous activities, evoked postsynaptic potentials and membrane properties of spiny neurons in rat neostriatum were compared before, during and after 5-8 min ischemia using intracellular recording and staining techniques in vivo. Severe forebrain ischemia was induced with the four-vessel occlusion method. Approximately 2.5 min after the onset of ischemia the baseline membrane potential quickly depolarized to -20 mV and remained at this level during ischemia. Repolarization began within 2 min after recirculation. The onset of ischemic depolarization was directly related to the severity of ischemia and its latency was inversely related to brain temperature. Spontaneous firing and membrane potential fluctuation of spiny neurons ceased immediately after ischemia and slowly recovered several hours after recirculation. No neuronal hyperactivity was observed up to 7 h after recirculation. Cortically evoked inhibitory postsynaptic potentials and late depolarizations disappeared earlier after ischemia and recovered later following recirculation than the initial excitatory postsynaptic potentials. Membrane input resistance of spiny neurons was significantly increased but the time constant remained the same following recirculation. The rheobase and spike threshold of spiny neurons were significantly increased and the repetitive firing evoked by depolarizing current pulse was suppressed shortly after recirculation. The results of the present study indicated that the spontaneous activity and evoked postsynaptic responses of spiny neurons are suppressed and the excitability of spiny neurons is decreased after transient ischemia. The polysynaptic responses are more sensitive to ischemia than the monosynaptic ones.

Activation of dopaminergic neurons modulates ventral pallidal responses evoked by Amygdala stimulation

The ventral pallidum is a basal forebrain region that is thought to integrate cognitive processes with motoric behaviors. These functions are influenced by ventral pallidal inputs, which include projections from the amygdala and the ventral tegmental area/substantia nigra zona compacta. By examining the consequences of this convergence at the neuronal level, the present study indicates that electrical activation of ventral tegmental regions releases dopamine in the ventral pallidum which subsequently modulates pallidal electrophysiological responses evoked by stimulating the amygdala. Stimulation-evoked responses were characterized for extracellular single unit recordings of spontaneously active ventral pallidal neurons from chloral hydrate anesthetized rats. Stimulation of the amygdala evoked short latency (⩽ 12 ms; possibly monosynaptic) and/or long latency (> 12 ms; polysynaptic) responses in all ventral pallidal neurons tested. Fifty-nine per cent of the tested neurons responded to ventral tegmental stimulation with short latency inhibition, and these neurons were often sensitive to microiontophoretically applied dopamine. Iontophoresis of dopamine antagonists SCH23390 (a Dl antagonist) or sulpiride (a D2 antagonist) attenuated the ventral tegmental-induced inhibitions. These observations indicate that the evoked responding was the result of endogenously released dopamine, and that D1 and D2 receptors were involved in this effect. Ninety-two per cent of the ventral pallidal neurons that demonstrated short latency responses to amygdala stimulation also exhibited short latency responses to activation of the ventral tegmentum. This suggests that these inputs often converge onto the same pallidal neurons. Amygdala-evoked responses were consistently attenuated by prior stimulation of the ventral tegmentum. Similarly, microiontophoretic ejection of dopamine attenuated amygdala-evoked effects. These results indicate that dopamine modulates amygdala-evoked pallidal responses. Such modulation may contribute to the integrative functions of the ventral pallidum.

NK1 and NK2 receptors contribute to C-fibre evoked slow potentials in the spinal cord.

Small diameter primary afferents produce slow synaptic potentials in spinal neurones. These can be recorded as prolonged ventral root potentials (VRPs) in the isolated neonatal rat spinal cord preparation. The VRP elicited by stimulating C-fibres consists of two phases: an early phase comprising a monosynaptic and a short polysynaptic response identical to that elicited by low threshold A beta fibres and a late phase which has an initial component (0.1-1 s) which is sensitive to N-methyl-D-aspartic acid receptor antagonism and a very long lasting second component (1-20 s) which is resistant to these antagonists. We now demonstrate that the slowest component of the VRP is significantly reduced by both NK1 and NK2 tachykinin receptor antagonists and as a consequence, tachykinins have a particular contribution to the cumulative depolarization produced by low frequency (1 Hz) C-fibre stimulation.

Altered desensitization produces enhancement of EPSPs in neocortical neurons

1. Neocortical brain slices were prepared from rats (35-50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.

The NMDA receptor antagonist CPP suppresses long-term potentiation in the rat hippocampal-accumbens pathway in vivo.

Excitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field potentials in the nucleus accumbens. When recorded in the dorsomedial aspect of the nucleus accumbens, the evoked field responses consisted of an early, negative-going component (N1) with a peak latency of 8-10 ms, followed by a second negative-going peak (N2) with a latency of 22-24 ms. The N1 response reflects monosynaptic activation of nucleus accumbens neurons; the N2 component appears to be polysynaptic in origin. In control rats, high-frequency stimulation of the fimbria (three trains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a long-lasting potentiation of both the N1 and N2 components. The magnitude of potentiation exhibited by the polysynaptic N2 response was typically greater than that of the monosynaptically evoked N1 response. Following delivery of the first train, the amplitude of the N1 and N2 components was increased by approximately 20 and 50% respectively. Administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP, 10 mg/kg i.p.) had no significant effects on the evoked nucleus accumbens responses. High-frequency stimulation failed to produce a significant increase in the amplitude of either the N1 or the N2 response when delivered 45-60 min after CPP administration. To test whether the suppressant effects of CPP were time-dependent, two further high-frequency trains were applied 90 and 180 min after administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Information processing within the motor cortex. I. Responses of morphologically identified motor cortical cells to stimulation of the somatosensory cortex.

Inputs from the somatosensory cortex to the motor cortex have been proposed to function in learning of motor skills. In an attempt to analyze how these somatosensory inputs were processed in the motor cortex, neurons in the superficial layer of the cat motor cortex were classified into three groups on the basis of synaptic responses elicited by intracortical microstimulation (ICMS) of area 2. ICMS was delivered through seven electrodes implanted in area 2. When ICMS through one of the seven sites produced a response that was greater than 50% of the response produced by stimulating the seven sites at a time, the site was called a "dominant" site. Type I cells were those that had a dominant stimulation site and showed a constant response latency when examined by a double shock test. Type II cells were those that had a dominant site but displayed a variable latency. Type III cells had no dominant site and showed a variable latency. Latency of type I responses was 1.2-2.6 milliseconds, which was much shorter than that of type II and type III responses. Seventy-nine neurons in layers II/III of the motor cortex, which responded to ICMS in area 2, were stained by intracellular injection of biocytin. From the presence of an apical dendrite and rich spines on the dendrites, 23 type I, 21 type II, and 15 type III cells were classified as pyramidal cells. Type II pyramidal cells were located more superficially than type I and type III pyramidal cells. On the basis of the absence or sparseness of dendritic spines, three type I and four type II cells in layers II/III were classified as nonpyramidal cells. These cells consisted of five small multipolar cells in layer II and a large multipolar cell and a small bitufted cell in layer III. The remaining 11 cells were not classified because of insufficient staining. Since type I and type II cells are considered to represent monosynaptic and polysynaptic responses to stimulation of area 2, respectively, information flow from type I cells to more superficially located type II cells is presumed in layers II/III of the motor cortex. Type III responses suggest the presence of a convergent flow of impulses inside of and/or between areas 2 and 4.

Omega-conotoxin sensitivity and presynaptic inhibition of glutamatergic sensory neurotransmission in vitro

Synaptic transmission between embryonic chick dorsal root ganglion (DRG) neurons and spinal cord neurons was studied in dissociated cell culture. Stimulation of DRG neurons evoked monosynaptic and polysynaptic excitatory responses in the spinal neurons. These responses could be reversibly blocked by application of 6-cyano-7-nitroquinoxaline-2,3-dione (a selective non-NMDA receptor antagonist) and irreversibly eliminated through the presynaptic action of omega-conotoxin GVIA (a selective N-type calcium channel antagonist). As N-type calcium channels in DRG neuron somata are targets for modulation via GABAB receptors, we tested the role of these receptors as regulators of synaptic transmission. Baclofen (a selective GABAB receptor agonist) reversibly inhibited synaptic transmission via a presynaptic, pertussis toxin-sensitive mechanism; CGP 35348 (a selective GABAB receptor antagonist) blocked the actions of baclofen. Taken together, these results demonstrate that N-type calcium channels play a dominant role in glutamatergic sensory neurotransmission. They suggest, in addition, that modulation of N-channel activity may underlie, at least in part, presynaptic inhibition of synaptic transmission between DRG neurons and their targets in the intact spinal cord.

Crossed and uncrossed segmental synaptic effects on rectus abdominis motoneurons from cutaneous and cutaneous-muscle nerve in spinal cats and alpha-chloralose-anesthetized cats.

Segmental synaptic responses evoked by stimulation of the dorsal cutaneous and cutaneous-muscle (CD) nerve or the ventral cutaneous and cutaneous-muscle (CV) nerve were investigated with intracellular recording from rectus abdominis (RA) motoneurons in 49 spinal cats and 28 alpha-chloralose-anesthetized cats. No monosynaptic and few disynaptic connections existed in the circuit from the ipsilateral or contralateral CD or CV nerves to RA motoneurons in spinal cats. Polysynaptic EPSP responses equal to or over trisynaptic connections were dominant. In alpha-chloralose-anesthetized cats, RA motoneurons exhibited significantly more polysynaptic EPSP responses at lower stimulus intensities (1.5T and 2T) of ipsilateral CV nerve stimulation than at those of contralateral CV nerve stimulation. The result that there was no monosynaptic or disynaptic PSP in RA motoneurons produced by low-intensity stimulation of the ipsilateral CD or CV nerve containing the cutaneous-muscle nerves indicated that Ia afferents from the cutaneous-muscle did not connect mono- or di-synaptically to the RA motoneuron. RA motoneurons exhibited more polysynaptic IPSP responses in alpha-chloralose-anesthetized cats than in spinal cats. Segmental pathways from the CD or CV nerves to RA motoneurons might receive inhibitory descending inputs from the upper spinal cord or the brain, in contrast to those from the same nerves to obliquus externus abdominis motoneurons previously reported.

Is 5-hydroxytryptamine mediating descending inhibition in the neonatal rat spinal cord through different receptor subtypes?

The long-lasting descending inhibition of lumbar segmental reflexes in the neonatal rat spinal cord has been investigated in vitro by recording from lumbar ventral roots on stimulation of a single lumbar dorsal root. Descending inhibition was elicited by a single stimulus to the latero-ventral thoracic cord. A number of strategies were used to clarify the role of 5-hydroxytryptamine (5-HT) in inhibiting the monosynaptic reflex, the ipsilateral polysynaptic response and the contralateral fast response evoked on the opposite side of the lumbar cord. The 5-HT uptake inhibitor, citalopram (10 nM), potentiated both short-interval (0.5–2 s) inhibition and long-interval (5–100 s) inhibition of the monosynaptic reflex, and also inhibition of the polysynaptic response 10–100 s after the thoracic stimulus. Inhibition of the monosynaptic reflex was blocked by ketanserin (1 μM), spiperone (1 μM) and methiothepin (1 μM), but not by spiroxatrine (0.1 μM) or sulpiride (1 μM). Sumatriptan (20 nM) and methysergide (10 nM) enhanced inhibition of the monosynaptic reflex 0.2–1 s after the thoracic stimulus. It was concluded that 5-HT acting through 5-HT 2A/2C receptors is the transmitter responsible for monosynaptic reflex inhibition, at intervals of 0.5–100 s, but a stronger stimulus to the thoracic cord may elicit a non-serotonergic component at intervals of 0.1–2 s. There was no unequivocal evidence that endogenous 5-HT activates 5-HT 1 receptors to produce inhibition. 5-HT acting through 5-HT 2A/2C receptors is also responsible for part of the inhibition of the polysynaptic response, but the transmitter(s) responsible for the ketanserin-resistant component of inhibition and for inhibition of the contralateral fast response has still to be identified.

The contributions of NMDA, non-NMDA, and GABA receptors to postsynaptic responses in neurons of the optic tectum

Activation of the NMDA subtype of glutamate receptor has been implicated in activity-dependent development and plasticity in several systems, including the retinotectal system of amphibians. To gain a better understanding of the response properties of tectal neurons, with particular emphasis on the role of both non-NMDA and NMDA glutamate receptors, we have developed an in vitro slice preparation of the diencephalon and midbrain of frog (Rana pipiens) tadpoles. In these slices, we electrically stimulated the optic tract and recorded both mono- and polysynaptic responses in single tectal neurons using whole-cell voltage clamp or current clamp. By including biocytin in the recording electrode, we were also able to determine the location and morphology of many of these neurons. Using these techniques, we found that the current-voltage (I-V) relations for both mono- and polysynaptic responses of tectal neurons showed voltage dependence only in the presence of extracellular Mg2+. This dependence reflects the hyperpolarization-dependent block of the NMDA channel by Mg2+. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist, reduced both mono- and polysynaptic responses of tectal neurons. Bath application of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL-APV) strongly reduced polysynaptic responses. When neurons were depolarized by the voltage clamp, relieving the Mg(2+)-dependent block of the NMDA channel, DL-APV application also reduced monosynaptic responses. Application of the GABAA receptor antagonist (-)bicuculline methiodide significantly increased the polysynaptic responses of tectal neurons, reflecting block of inhibition. We further confirmed the presence of these three types of receptors by examining postsynaptic currents evoked by iontophoretic application of the three agonists, NMDA, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and GABA. These results confirm that the dominant excitatory transmitter in the tectum appears to be glutamate. Furthermore, the retinotectal synapses (i.e., monosynaptic currents) express functional NMDA receptors that are voltage dependent and are not responsible for the bulk of normal excitatory transmission. Polysynaptic responses, however, are mediated by both non-NMDA and NMDA receptors, and inhibition plays a significant role in sculpting these polysynaptic responses.

Alterations in both excitation and inhibition occur before the onset of seizure activity in the hippocampus

Excitatory and inhibitory mechanisms have been implicated in the onset of seizures and as underlying kindling. In this study, changes in responses to single stimuli and paired pulse stimuli were used to monitor postsynaptic excitability before the onset of seizure activity in limbic circuits of urethane-anesthetized rats. With sufficient stimulus intensity, a stimulus paradigm of seven pulses every second for 10 s led to seizure activity, as indicated by the appearance of maximal dentate activation, and afterdischarges. An increase in the evoked response was found in both CA1 and the dentate gyrus during stimulus trains to either CA3 or the angular bundle and there was the appearance of a polysynaptic response. There was an increase in paired pulse inhibition in the dentate gyrus and a decrease in paired pulse inhibition in the CA1 region during the stimulus protocol. Since repeated seizures and a number of pharmacological agents are known to alter the onset and duration of seizure activity, a relationship between the changes in excitability and the onset of the seizure activity was tested using MK-801, ketamine, bicuculline, diazepam, phenobarbital, baclofen and repeated seizures. Overall, alteration of the amplitude of the polysynaptic response in CA1 to angular bundle stimulation correlated best with the effects of the drugs and the seizures on the duration of maximal dentate activation.

Spinal input to thalamic VL neurons: evidence for direct spinothalamic effects.

1. The postsynaptic actions of afferents ascending in the ventrolateral quadrant and dorsal columns of the spinal cord were studied in neurons in the ventrolateral nucleus of the thalamus (VL) (n = 138) by use of intracellular recording procedures. Neurons were identified by their monosynaptic input from the cerebellum and, when possible, their antidromic activation from the motor cortex. The possible occurrence of monosynaptic transmission along spinothalamic fibers was investigated by estimating the intrathalamic delay time of postsynaptic responses and by examining the occurrence of temporal facilitation to double-shock stimulation. The experiments were performed in cats anesthetized with alpha-chloralose. 2. The majority of neurons (86%) responded with excitatory or inhibitory postsynaptic potentials to stimulation of the ascending paths. The response latencies of excitation on stimulation of the ventral quadrants at C3 ranged from 2.9 to 18 ms. Evidence for monosynaptic excitation after stimulation of (spinothalamic) afferents ascending in the ventrolateral quadrants was obtained for a number of neurons (n = 30). For these neurons, estimated intrathalamic delays were less than 1 ms and/or the neurons did not display temporal facilitation to double shocks. All the shortest latency responses (from C3) showed evidence of monosynaptic transmission. It is estimated that approximately 19-39% of neurons sampled may receive monosynaptic input. The spinal conduction velocities of the direct projections ranged from 10 to 35 m/s (median 20 m/s). 3. Much of the ascending input was mediated polysynaptically. For afferents ascending in the ventrolateral quadrant, estimated intrathalamic delays were greater than 1.5 ms and/or the postsynaptic responses displayed temporal facilitation to double shocks. The shortest latency from C3 of a polysynaptic response was 5 ms. Spatial interactions were observed between polysynaptic inputs from the ventrolateral quadrants and the dorsal columns, indicating that at least some of the pathways to VL are shared. 4. The data show that many neurons in the VL receive input ascending from the spinal cord via direct and indirect routes. Somatosensory information reaching VL could serve to adjust, during the course of movement execution, the cerebellar commands relayed by VL to the motor cortex.

A functional microcircuit for cat visual cortex.

1. We have studied in vivo the intracellular responses of neurones in cat visual cortex to electrical pulse stimulation of the cortical afferents and have developed a microcircuit that simulates much of the experimental data. 2. Inhibition and excitation are not separable events, because individual neurones are embedded in microcircuits that contribute strong population effects. Synchronous electrical activation of the cortex inevitably set in motion a sequence of excitation and inhibition in every neurone we recorded. The temporal form of this response depends on the cortical layer in which the neurone is located. Superficial layer (layers 2+3) pyramidal neurones show a more marked polysynaptic excitatory phase than the pyramids of the deep layers (layers 5+6). 3. Excitatory effects on pyramidal neurones, particularly the superficial layer pyramids, are in general not due to monosynaptic input from thalamus, but polysynaptic input from cortical pyramids. Since the thalamic input is transient it does not provide the major, sustained excitation arriving at any cortical neurone. Instead the intracortical excitatory connections provide the major component of the excitation. 4. The polysynaptic excitatory response would be sustained well after the stimulus, were it not for the suppressive effect of intracortical inhibition induced by the pulse stimulation. 5. Intracellular recording combined with ionophoresis of gamma-aminobutyric acid (GABA) agonists and antagonists showed that intracortical inhibition is mediated by GABAA and GABAB receptors. The GABAA component occurs in the early phase of the impulse response. It is reflected in the strong hyperpolarization that follows the excitatory response and lasts about 50 ms. The GABAB component occurs in the late phase of the response, and is reflected in a sustained hyperpolarization that lasts some 200-300 ms. Both components are seen in all cortical pyramidal neurones. However, the GABAA component appears more powerful in deep layer pyramids than superficial layer pyramids. 6. The microcircuit simulates with good fidelity the above data from experiments in vivo and provides a novel explantation for the apparent lack of significant inhibition during visual stimulation. The basic circuit may be common to all cortical areas studied and thus the microcircuit may be a 'canonical' microcircuit for neocortex.