Late Excitatory Postsynaptic Potential Research Articles

Differences in Ia proprioceptive input to spinal motoneurons between male and female rats.

Male and female rats differ in muscle fibre composition, related motor unit contractile properties, and muscle spindle density but not number. On the other hand, their motoneurons' intrinsic properties, excitability and firing properties are similar. The aim of this study was to investigate whether apparent sex differences in body mass and muscle force influence the proprioceptive input from muscle spindles to motoneurons. Medial gastrocnemius motoneurons were investigated intracellularly in deeply anaesthetised male and female rats. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked using electrical stimulation of primary afferents from homonymous muscle. Data were analysed using a mixed linear model. The central latencies of EPSPs were 0.38-0.80 ms, with no differences in means between males and females. The maximum EPSP amplitude varied between 2.03 and 8.09 mV in males and 1.24 and 6.79 mV in females. The mean maximum EPSP amplitude was 26% higher in males than in females. The mean EPSP rise time, half-decay time and total duration did not differ between the sexes. EPSP amplitudes correlated with the resting membrane potential, input resistance and EPSP rise time in both sexes. The observed sex differences in the Ia proprioceptive input may be related either to mechanical loading differences in males and females associated with their different body mass or hormonal differences influencing the levels of neuromodulation in spinal circuits. The results highlight the importance of taking sex into consideration in the studies on the influence of afferent inputs on MN excitability.

Cortical Stimulation Induces Excitatory Postsynaptic Potentials of Inferior Colliculus Neurons in a Frequency-Specific Manner.

Corticofugal modulation of auditory responses in subcortical nuclei has been extensively studied whereas corticofugal synaptic transmission must still be characterized. This study examined postsynaptic potentials of the corticocollicular system, i.e., the projections from the primary auditory cortex (AI) to the central nucleus of the inferior colliculus (ICc) of the midbrain, in anesthetized C57 mice. We used focal electrical stimulation at the microampere level to activate the AI (ESAI) and in vivo whole-cell current-clamp to record the membrane potentials of ICc neurons. Following the whole-cell patch-clamp recording of 88 ICc neurons, 42 ICc neurons showed ESAI-evoked changes in the membrane potentials. We found that the ESAI induced inhibitory postsynaptic potentials in 6 out of 42 ICc neurons but only when the stimulus current was 96 μA or higher. In the remaining 36 ICc neurons, excitatory postsynaptic potentials (EPSPs) were induced at a much lower stimulus current. The 36 ICc neurons exhibiting EPSPs were categorized into physiologically matched neurons (n = 12) when the characteristic frequencies of the stimulated AI and recorded ICc neurons were similar (≤1 kHz) and unmatched neurons (n = 24) when they were different (>1 kHz). Compared to unmatched neurons, matched neurons exhibited a significantly lower threshold of evoking noticeable EPSP, greater EPSP amplitude, and shorter EPSP latency. Our data allow us to propose that corticocollicular synaptic transmission is primarily excitatory and that synaptic efficacy is dependent on the relationship of the frequency tunings between AI and ICc neurons.

Polysynaptic connections between Barrington's nucleus and sacral preganglionic neurons

The pontine micturition center, or Barrington's nucleus, is an essential component in the micturition reflex. The purpose of the present study is to examine the connections between Barrington's nucleus and sacral preganglionic neurons with an electrophysiological method using an intracellular recording technique. When the bladder pressure was near 0mmH2O, electrical stimulation of Barrington's nucleus either evoked no postsynaptic potential or evoked very small excitatory postsynaptic potentials (EPSPs) with ambiguous onset, in sacral preganglionic neurons. However, when the bladder showed micturition contraction, electrical stimulation of the nucleus evoked clear EPSPs in sacral preganglionic neurons. Latencies of EPSPs ranged from 21.9 to 47.5ms. The onset of the EPSPs was not fixed in any of the preganglionic neurons, indicating that they were evoked polysynaptically. The results thus demonstrated that the descending pathway from Barrington's nucleus to the sacral preganglionic neurons is polysynaptic. The results also showed that the descending pathway is strongly facilitated during the voiding phase, whereas this facilitatory effect is very weak when the bladder pressure is low. The study supports the idea that continuous firings of Barrington's nucleus are needed to activate the sacral preganglionic neurons that innervate the bladder muscle.

Loss of olfactory cell adhesion molecule reduces the synchrony of mitral cell activity in olfactory glomeruli

Odours generate activity in olfactory receptor neurons, whose axons contact the dendritic tufts of mitral cells within olfactory bulb glomeruli. These axodendritic synapses are anatomically separated from dendrodendritic synapses within each glomerulus. Mitral cells within a glomerulus show highly synchronized activity as assessed with whole-cell recording from pairs of mitral cells. We examined glomerular activity in mice lacking the olfactory cell adhesion molecule (OCAM). Glomeruli in mice lacking OCAM show a redistribution of synaptic subcompartments, but the total area occupied by axonal inputs was similar to wild-type mice. Stimulation of olfactory nerve bundles showed that excitatory synaptic input to mitral cells as well as dendrodendritic inhibition was unaffected in the knockout. However, correlated spiking in mitral cells was significantly reduced, as was electrical coupling between apical dendrites. To analyse slow network dynamics we induced slow oscillations with a glutamate uptake blocker. Evoked and spontaneous slow oscillations in mitral cells and external tufted cells were broader and had multiple peaks in OCAM knockout mice, indicating that synchrony of slow glomerular activity was also reduced. To assess the degree of shared activity between mitral cells under physiological conditions, we analysed spontaneous sub-threshold voltage oscillations using coherence analysis. Coherent activity was markedly reduced in cells from OCAM knockout mice across a broad range of frequencies consistent with a decrease in tightly time-locked activity. We suggest that synchronous activity within each glomerulus is dependent on segregation of synaptic subcompartments.

Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of absence seizures

We used sharp-electrode, intracellular recordings in an in vitro brain slice preparation to study the excitability of neocortical neurons located in the deep layers (>900 microm from the pia) of epileptic (180-210-days old) Wistar Albino Glaxo/Rijswijk (WAG/Rij) and age-matched, non-epileptic control (NEC) rats. Wistar Albino Glaxo/Rijswijk rats represent a genetic model of absence seizures associated with generalized spike and wave (SW) discharges in vivo. When filled with neurobiotin, these neurons had a typical pyramidal shape with extensive apical and basal dendritic trees; moreover, WAG/Rij and NEC cells had similar fundamental electrophysiological and repetitive firing properties. Sequences of excitatory postsynaptic potentials (EPSPs) and hyperpolarizing inhibitory postsynaptic potentials (IPSPs) were induced in both the strains by electrical stimuli delivered to the underlying white matter or within the neocortex; however, in 24 of 55 regularly firing WAG/Rij cells but only in 2 of 25 NEC neurons, we identified a late EPSP that (1) led to action potential discharge and (2) was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (20 microM; n = 8/8 WAG/Rij cells). Finally, we found that the fast and slow components of the stimulus-induced IPSPs recorded during the application of glutamatergic receptor antagonists had similar reversal potentials in the two strains, while the peak conductance of the fast IPSP was significantly reduced in WAG/Rij cells. These findings document an increase in synaptic excitability that is mediated by NMDA receptors, in epileptic WAG/Rij rat neurons located in neocortical deep layers. We propose that this mechanism may be instrumental for initiating and maintaining generalized SW discharges in vivo.

Bidirectional shift in the cornu ammonis 3 pyramidal dendritic organization following brief stress

The negative impact of chronic stress at the structure of apical dendrite branches of cornu ammonis 3 (CA3) pyramidal neurons is well established. However, there is no information available on the CA3 dendritic organization related to short-lasting stress, which suffices to produce long-term habituation or sensitization of anxiety behaviors and neuroendocrine responses. Here, we tested the effects evoked by brief stress on the arrangements of CA3 pyramidal neuron dendrites, and the activity-dependent properties of the commissural-associational (C/A) excitatory postsynaptic potentials (EPSPs). Adult male rats were socially defeated followed by 3 weeks without further treatment or as comparison exposed to a regimen of a social defeat every second day for the same time period. We assessed CA3 pyramidal neurons with somatic whole-cell recording and neurobiotin application in acute hippocampal slices. The results from morphometric analysis of post hoc reconstructions demonstrated that CA3 dendrites from repeatedly stressed rats were reduced in surface area and length selectively at the apical cone (70% of control, approximately 280 μm from the soma). Brief stress, however, produced a similar decrease in apical dendritic length (77% of control, approximately 400 μm from the soma), accompanied by an increased length (167% of control) and branch complexity at the basal cone. The structural changes of the dendrites significantly influenced signal propagation by shortening the onset latency of EPSPs and increasing input resistance ( r=0.45, P<0.01), of which the first was significantly changed in repeatedly stressed animals. Both brief and repeated stress long-lastingly impaired long-term potentiation of C/A synapses to a similar degree ( P<0.05). These data indicate that the geometric plasticity of CA3 dendrites is dissociated from repetition of aversive experiences. A double social conflict suffices to drive a dynamic reorganization, by site-selective elimination and de novo growth of dendrite branches over the course of weeks after the actual experience.

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study.

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20 ms and 33 ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cells.

Synaptic inputs from low threshold afferents of trunk muscles to motoneurons innervating the longissimus lumborum muscle in the spinal cat.

(1) We studied the reflex actions of group I and II afferents to longissimus lumborum (Long) motoneurons in the L1-L5 spinal segments from the epaxial muscle, m. Long, and the hypaxial muscle, m. obliquus externus abdominus (OEA). (2) Postsynaptic potentials (PSPs) recorded from 140 Long motoneurons in 30 spinal cats were analyzed. Under the present experimental conditions, the stimulation of Long and OEA nerves at an intensity below 1.5 times threshold (T) activated only group I muscle afferents, while stimulations at 2-5T activated group II muscle afferents as well. (3) The incidence of PSPs was related to the proximity of the spinal segments of the nerves stimulated to the spinal segment of the motoneurons; the shorter the distance the larger the PSPs and higher incidence of PSPs. The Long motoneurons received group I afferent input mainly from the same and adjacent segments, and received group II afferent inputs from a wider range of segments. (4) A short (i.e., less than 1.0 ms) latency of excitatory PSPs (EPSPs) evoked by ipsilateral group I afferents of Long at the same or adjacent segment indicated a monosynaptic connection. In general, the central latencies became longer as the distance between spinal segments of stimulated nerves and motoneurons increased. Major PSP components were produced by polysynaptic neuronal pathways. The spatial facilitation between PSPs evoked by afferents of different nerves (i.e., ipsilateral Long (iLong) and contralateral Long (cLong) of the same segment; iLongs of different segments; and iLong and iOEA of the same segment) indicated that they shared common interneurons. (5) Although iLong and iOEA muscle afferents produced predominantly EPSPs, and contralateral muscle afferents elicited predominantly IPSPs in Long motoneurons at each spinal segment, the patterns of convergence from Long and OEA muscle afferents of different spinal segments and of different sides differed considerably among motoneurons. (6) These findings demonstrated various input patterns of individual motoneurons within the same motoneuron pool, which might reflect the complexity of neuronal control of the back muscles for various trunk movements, including lateral and dorsal bending, rotating, and fixation of the trunk.

Potentially epileptogenic dysfunction of cortical NMDA- and GABA-mediated neurotransmission in Otx1-/- mice.

Knockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures. We investigated the excitable properties of layer V pyramidal neurons in neocortical slices prepared from Otx1-/- mice and age-matched controls. The qualitative firing properties of the neurons of Otx1-/- mice were identical to those found in wild-type controls, but the proportion of intrinsically bursting (IB) neurons was significantly smaller. This is in line with the lack of the Otx1 gene contribution to the generation and differentiation of neurons destined for the deep neocortical layers, in which IB neurons are located selectively in wild-type rodents. The pyramidal neurons recorded in Otx1-/- mice responded to near-threshold electrical stimulation of the underlying white matter, with aberrant polysynaptic excitatory potentials often leading to late action potential generation. When the strength of the stimulus was increased, the great majority of the Otx1-/- neurons (78%) responded with a prominent biphasic inhibitory postsynaptic potential that was significantly larger than that observed in the wild-type mice, and was often followed by complex postinhibitory depolarizing events. Both late excitatory postsynaptic potentials and postinhibitory excitation were selectively suppressed by NMDA receptor antagonists, but not by AMPA antagonists. We conclude that the cortical abnormalities of Otx1-/- neocortex due to a selective loss of large projecting neurons lead to a complex rearrangement of local circuitry, which is characterized by an excess of N-methyl-d-aspartate-mediated polysynaptic excitation that is counteracted by GABA-mediated inhibition in only a limited range of stimulus intensity. Prominent postsynaptic inhibitory potentials may also act as a further pro-epileptogenic event by synchronizing abnormal excitatory potentials.

Enhanced excitatory synaptic transmission in spiny neurons of rat striatum after unilateral dopamine denervation

The synaptic transmission and intrinsic membrane properties of spiny neurons in rat neostriatum were studied after unilateral dopamine depletion using in vivo intracellular recording and staining techniques. Two to four weeks after dopamine denervation, the spontaneous firing rate of spiny neurons increased and the spontaneous membrane potential fluctuation stayed at a more depolarized state for longer periods of time. The amplitude of cortically evoked initial excitatory postsynaptic potentials increased and a late excitatory postsynaptic potential that was occasionally found in control neurons was elicited from 23% of spiny neurons after dopamine denervation. No significant changes in intrinsic membrane properties of spiny neurons were observed after dopamine denervation. These results suggest that dopamine inhibits excitatory synaptic transmission of spiny neurons in naı̈ve animals.

Network activity evoked by neocortical stimulation in area 36 of the guinea pig perirhinal cortex.

The perirhinal cortex is a key structure involved in memory consolidation and retrieval. In spite of the extensive anatomical studies that describe the intrinsic and extrinsic associative connections of the perirhinal cortex, the activity generated within such a network has been poorly investigated. We describe here the pattern of synaptic interactions that subtend the responses evoked in area 36 of the perirhinal cortex by neocortical and local stimulation. The experiments were carried out in the in vitro isolated guinea pig brain. The synaptic perirhinal circuit was reconstructed by integrating results obtained during intracellular recordings from layer II-III neurons with simultaneous current source density analysis of laminar profiles performed with 16-channel silicon probes. Both neocortical and local stimulation of area 36 determined a brief monosynaptic excitatory potential in layer II-III neurons, followed by a biphasic synaptic inhibitory potential possibly mediated by a feed-forward inhibitory circuit at sites close to the stimulation electrode and a late excitatory postsynaptic potential (EPSP) that propagated at distance within area 36 along the rhinal sulcus. During a paired-pulse stimulation test, the inhibitory postsynaptic potential (IPSP) and the late EPSP were abolished in the second conditioned response, suggesting that they are generated by poli-synaptic circuits. Current source density analysis of the field responses demonstrated that 1) the monosynaptic activity was generated in layers II-III and 2) the sink associated to the disynaptic responses was localized within the superficial layer of area 36. We conclude that the neocortical input induces a brief monosynaptic excitation in area 36 of the perirhinal cortex, that is curtailed by a prominent inhibition and generates a recurrent excitatory associative response that travels at distance within area 36 itself. The results suggest that the perirhinal cortex network has the potentials to integrate multimodal incoming neocortical information on its way to the hippocampus.

Synaptic transmission in the neocortex during reversible cooling

We studied the effects of reversible cooling on synaptic transmission in slices of rat visual cortex. Cooling had marked monotonic effects on the temporal properties of synaptic transmission. It increased the latency of excitatory postsynaptic potentials and prolonged their time-course. Effects were non-monotonic on other properties, such as amplitude of excitatory postsynaptic potentials and generation of spikes. The amplitude of excitatory postsynaptic potentials increased, decreased, or remain unchanged while cooling down to about 20°C, but thereafter it declined gradually in all cells studied. The effect of moderate cooling on spike generation was increased excitability, most probably due to the ease with which a depolarized membrane potential could be brought to spike threshold by a sufficiently strong excitatory postsynaptic potential. Stimuli that were subthreshold above 30°C could readily generate spikes at room temperature. Only at well below 10°C could action potentials be completely suppressed. Paired-pulse facilitation was less at lower temperatures, indicating that synaptic dynamics are different at room temperature as compared with physiological temperatures. These results have important implications for extrapolating in vitro data obtained at room temperatures to higher temperatures. The data also emphasize that inactivation by cooling might be a useful tool for studying interactions between brain regions, but the data recorded within the cooled area do not allow reliable conclusions to be drawn about neural operations at normal temperatures.

Chapter 13 A Positive Feedback Circuit Involving Muscle Spindle Secondaries and Gamma Motoneurons in the Cat

Publisher Summary Many negative feedback neuronal circuits are known in the mammalian nervous system. Negative feedback is represented, for example, by recurrent inhibition of motoneurons through their axon collaterals and Renshaw cells, by recurrent inhibition of several other neurons, or by autogenetic inhibition of motoneurons following contractions of the muscles that they innervate. Examples of a clear-cut positive feedback are more difficult to find; in a recent review on proprioceptive feedback and movement regulation, positive feedback was mentioned only once and only in the context of force feedback. An effective positive feedback would require the connection between muscle spindle afferents and γ-motoneurons to be as direct as possible, preferably to be monosynaptic. Previous studies led to the conclusion that group II afferents excite γ-motoneurons only through di-, tri-, or even polysynaptic pathways because of the rather long latencies of their actions. Latencies of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) evoked in α-motoneurons by electrical stimulation of group II afferents in muscle nerves were similarly classified as polysynaptically evoked. A number of subsequent observations have, however, shown that at least some synaptic actions of group II muscle afferents on α-motoneurons might be evoked di-synaptically or even mono-synaptically.

Golgi cells in the superficial granule cell domain overlying the ventral cochlear nucleus: Morphology and electrophysiology in slices

Golgi cells are poised to integrate multimodal influences by participating in circuits involving granule cells in the cochlear nuclei. To understand their physiological role, intracellular recordings were made from anatomically identified Golgi cells in slices of the cochlear nuclei from mice. Cell bodies, dendrites, and terminals for all seven labeled cells were restricted to the narrow plane of the superficial granule cell domain over the ventral cochlear nucleus. The axonal arborization was the most striking feature of all Golgi cells; a dense plexus of terminals covered an area 200-400 microm in diameter in the vicinity of the cell body and dendrites. Axonal beads often surrounded granule cell bodies, indicating that granule cells are probable targets. Cells had input resistances up to 130 M omega and fired regular, overshooting action potentials. Golgi cells probably receive auditory nerve input, because shocks to the cut end of the auditory nerve excited Golgi cells with excitatory postsynaptic potentials (EPSPs). The latency of EPSPs shortened to a minimum and the amplitude of EPSPs grew in several steps as the strength of shocks was increased. The minimum latency of EPSPs in Golgi cells was on average 1.3 milliseconds, 0.6 milliseconds longer than the minimum latencies of EPSPs in nearby octopus and T stellate cells. The long latency raises the possibility that Golgi cells receive input from slowly conducting, unmyelinated auditory nerve fibers. Golgi cells are also excited by interneurons with N-methyl-D-aspartate receptors, probably granule cells, because repetitive shocks and single shocks in the absence of extracellular Mg2+ evoked late EPSPs that were reversibly blocked by DL-2-amino-5-phosphono-valeric acid.

Synaptic inputs to stellate cells in the ventral cochlear nucleus.

Auditory information is carried from the cochlear nuclei to the inferior colliculi through six parallel ascending pathways, one of which is through stellate cells of the ventral cochlear nuclei (VCN) through the trapezoid body. To characterize and identify the synaptic influences on T stellate cells, intracellular recordings were made from anatomically identified stellate cells in parasagittal slices of murine cochlear nuclei. Shocks to the auditory nerve consistently evoked five types of synaptic responses in T stellate cells, which reflect sources intrinsic to the cochlear nuclear complex. 1) Monosynaptic excitatory postsynaptic potentials (EPSPs) that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, probably reflected activation by auditory nerve fibers. Electrophysiological estimates indicate that about five auditory nerve fibers converge on one T stellate cell. 2) Disynaptic, glycinergic inhibitory postsynaptic potentials (IPSPs) arise through inhibitory interneurons in the VCN or in the dorsal cochlear nucleus (DCN). 3) Slow depolarizations, the source of which has not been identified, that lasted between 0.2 and 1 s and were blocked by -2-amino-5-phosphonovaleric acid (APV), the N-methyl-D-aspartate (NMDA) receptor antagonist. 4) Rapid, late glutamatergic EPSPs are polysynaptic and may arise from other T stellate cells. 5) Trains of late glycinergic IPSPs after single or repetitive shocks match the responses of D stellate cells, showing that D stellate cells are one source of glycinergic inhibition to T stellate cells. The source of late, polysynaptic EPSPs and IPSPs was assessed electrophysiologically and pharmacologically. Late synaptic responses in T stellate cells were enhanced by repetitive stimulation, indicating that the interneurons from which they arose should fire trains of action potentials in responses to trains of shocks. Late EPSPs and late IPSPs were blocked by APV and enhanced by the removal of Mg2+, indicating that the interneurons were driven at least in part through NMDA receptors. Bicuculline, a gamma-aminobutyric acid-A (GABAA) receptor antagonist, enhanced the late PSPs, indicating that GABAergic inhibition suppresses both the glycinergic interneurons responsible for the trains of IPSPs in T-stellate cells and the interneuron responsible for late EPSPs in T stellate cells. The glycinergic interneurons that mediate the series of IPSPs are intrinsic to the ventral cochlear nucleus because long series of IPSPs were recorded from T stellate cells in slices in which the DCN was removed. These experiments indicate that T stellate cells are a potential source of late EPSPs and that D stellate cells are a potential source for trains of late IPSPs.

Direct and indirect corticospinal control of arm and hand motoneurons in the squirrel monkey (Saimiri sciureus).

Anatomic evidence suggests that direct corticomotoneuronal (CM) projections to hand motoneurons in the New World squirrel monkey (Saimiri sciureus) are weak or absent, but electrophysiological evidence is lacking. The nature of the corticospinal linkage to these motoneurons was therefore investigated first with the use of transcranial magnetic stimulation (TMS) of the motor cortex under ketamine sedation in five monkeys. TMS produced early responses in hand muscle electromyogram, but thresholds were high (compared with macaque monkey) and the onset latency was variable. Second, stimulation of the pyramidal tract (PT) was carried out with the use of chronically implanted electrodes in ketamine-sedated monkeys; this produced more robust responses that were markedly facilitated by repetitive stimulation, with little decrease in latency on the third compared with the first shock. Finally, postsynaptic potentials were recorded intracellularly from 93 arm and hand motoneurons in five monkeys under general chloralose anesthesia. After a single PT stimulus, the most common response was a small, slowly rising excitatory postsynaptic potential (EPSP), either alone (35 of 93 motoneurons) or followed by an inhibitory postsynaptic potential (39 of 93). The segmental delay of the early EPSPs was within the monosynaptic range (mean 0.85 ms); however, the rise time of these EPSPs was slow (mean 1.3 ms) and their amplitude was small (mean 0.74 mV). These values are significantly slower and smaller than EPSPs in a comparable sample of Old World macaque monkey motoneurons. The results show that CM connections do exist in the squirrel monkey but that they are weak and possibly located on the remote dendrites of the motoneurons. The findings are consistent with earlier anatomic studies. Repetitive PT stimulation produced large, late EPSPs in some motoneurons, suggesting that, in this species, there are relatively strong nonmonosynaptic pathways linking the corticospinal tract to hand motoneurons.

Convergent chemical and electrical synaptic inputs from proprioceptive afferents onto an identified intersegmental interneuron in the crayfish.

Synaptic transmission between proprioceptive afferents from a chordotonal organ in the tailfan of the crayfish and an identified ascending interneuron, interneuron A, in the terminal abdominal ganglion was analyzed. Interneuron A is part of a disynaptic pathway from primary afferent neurons to the lateral giant interneuron involved in producing the characteristic ballistic escape behavior of crayfish. Interneuron A received short and long latency excitatory postsynaptic potentials (EPSPs) from chordotonal afferents. Short latency EPSPs occurred with little central synaptic delay, were unchanged by hyperpolarizing current injection of -2 nA, and remained at a constant amplitude when the nervous system was bathed in saline with a low calcium concentration or saline containing the nicotinic antagonist curare. These EPSPs are thus thought to be mediated by electrical transmission. Longer latency potentials were increased in amplitude by hyperpolarizing current injection, reduced in amplitude when the nervous system was bathed in low-calcium saline, and also reduced by bath application of saline containing curare. These potentials are thus thought to be mediated by chemical transmission. The functional significance of the dual modes of transmission at a key synapse in the escape circuitry is discussed.

Synaptic excitation in the dorsal nucleus of the lateral lemniscus: whole-cell patch-clamp recordings from rat brain slice

The synaptic events underlying the excitation of neurons in the rat's dorsal nucleus of the lateral lemniscus were studied by whole-cell patch-clamp recordings in a brain slice preparation of the auditory midbrain. Both current-clamp and voltage-clamp data were obtained with the brain slice submerged in artificial cerebrospinal fluid. The rats were between 21 and 35days of age at the time the recordings were made. Synaptic responses were evoked by a bipolar stimulating electrode placed on the lateral lemniscus just ventral to the dorsal nucleus. To eliminate glycinergic inhibitory responses, all physiological data were gathered with 0.5μM strychnine added to the saline bath. Under current-clamp conditions, excitatory postsynaptic potentials could be subdivided into early and late components. The early component produced a single, highly reliable, short-latency spike and the later component produced a more variable, long-latency spike or train of spikes. The non-N-methyl-d-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, completely blocked the early excitatory postsynaptic potential and its associated action potential. The N-methyl-d-aspartate antagonist, d,l-2-amino-5-phosphonovaleric acid, blocked the later excitatory postsynaptic potential and its action potentials. Typically, both early and late excitatory postsynaptic potentials could be recorded from the same cell, but the early excitatory postsynaptic potential was evoked at lower stimulus levels and had a larger amplitude than the later excitatory postsynaptic potential. Under voltage-clamp conditions, dorsal nucleus of the lateral lemniscus neurons responded to stimulation of the lateral lemniscus with excitatory postsynaptic currents. Outward excitatory postsynaptic currents were recorded with holding potentials that depolarized the cell membrane and inward currents were seen when the cell was hyperpolarized. The current–voltage (I–V) relation of the early peak portion of the excitatory postsynaptic current was nearly linear, whereas the I–V relation of the later excitatory postsynaptic current (12ms after the peak) was non-linear over the range between −50 and −100mV. The outward excitatory postsynaptic current consisted of an early current that was selectively blocked by 6-cyano-7-nitroquinoxaline-2,3-dione and a later current that was blocked by d,l-2-amino-5-phosphonovaleric acid. In artificial cerebrospinal fluid with normal concentrations of Mg2+, the inward excitatory postsynaptic current was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, but was not affected by d,l-2-amino-5-phosphonovaleric acid. In Mg2+-free artificial cerebrospinal fluid, however, the early component of the inward excitatory postsynaptic current was selectively blocked by 6-cyano-7-nitroquinoxaline-2,3-dione and a later component was blocked by d,l-2-amino-5-phosphonovaleric acid.The results indicate that both N-methyl-d-aspartate and non-N-methyl-d-aspartate receptor-mediated synaptic responses are present in dorsal nucleus of the lateral lemniscus neurons of rats at 21–35days of age. The N-methyl-d-aspartate component had a longer time-course and a higher threshold than the non-N-methyl-d-aspartate component, and was subject to a voltage-dependent Mg2+ block when the cell's membrane was hyperpolarized. The long-duration N-methyl-d-aspartate component is probably responsible for the prolonged inhibitory effect of dorsal nucleus of the lateral lemniscus neurons on physiological responses in the rat's inferior colliculus.

Patterns of inputs to the parietal cortex efferent neurons from the motor cortex and cerebellum in the cat

Responses of parietal association cortex efferent neurons to motor cortex and cerebellar nuclei stimulation were studied intracellularly in anaesthetized cats. Efferent neurons of the parietal cortex were identified according to their antidromic activation on stimulation of the motor cortex, pontine nuclei proper and red nucleus. Monosynaptic excitatory postsynaptic potentials of ipsilateral anterior suprasylvian and lateral gyri neurons to motor cortex stimulation have been established. Oligo- and polysynaptic excitatory responses of parietal cortex efferent neurons to cerebellar nuclei stimulation have been recorded. Correlation between the latencies of cerebellar-induced excitatory postsynaptic potentials and antidromic invasion of neurons on stimulation of different parietal cortex efferent projections (corticocortical, corticopontine, corticorubral) has been obtained. A similar correlation has been found between the latencies of excitatory postsynaptic potentials evoked on stimulation of one of the cerebellar nuclei and latencies of antidromic invasion induced on stimulation of all studied parietal cortex efferent systems. Feedforward and feedback mechanisms in the input–output organization of parietal association cortex have been discussed.

Long-term potentiation of supragranular pyramidal outputs in the rat auditory cortex

In supragranular layers of the rat auditory cortex, white matter stimulation produces antidromic and transsynaptic field potentials, of which only the latter shows long-term potentiation (LTP) following tetanic stimulation of the white matter. In this study, we investigated the cells responsible for the LTP. The transsynaptic field potentials, excitatory postsynaptic potentials (EPSPs), and orthodromic spikes were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), but not by D-2-amino-5-phosphonovalerate (D-AP5, 50 microM). The latency of EPSPs was constant, while that of transsynaptic field potentials and orthodromic spikes was shortened by the increase in stimulus intensity. Appearance of antidromic field potentials and antidromic spikes at strong stimulus intensities were accompanied by reduction in amplitude of transsynaptic field potentials and elimination of orthodromic spikes, respectively. Morphological identification of neurons showing antidromic spikes by intracellular injection of biocytin revealed that most of them were supragranular pyramidal cells. The effects of tetanic stimulation were studied by intracellular recording in seven neurons showing antidromic spikes, and it was found that only two of them showed LTP of EPSP slope. However, in all of the other eight units showing antidromic spikes and recorded extracellularly, LTP was clearly observed in orthodromic firing probability. The LTP induction in the orthodromic firing probability was blocked by D-AP5. These findings indicate that the LTP in field potentials corresponds to LTP in supragranular pyramidal outputs, and the input-output relationship in neural networks of the adult rat auditory cortex is strongly modulated by LTP.