EPSP Amplitude Research Articles

Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys.

BackgroundAnesthetic-induced CNS depression is thought to involve reduction of glutamate release from nerve terminals. Recent studies suggest that isoflurane reduces glutamate release by block of Na channels. To further investigate this question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and stimulus voltage (stim) on glutamate-mediated transmission at hippocampal excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal brain slices in response to Schaffer-collateral fiber stimulation.ResultsIsoflurane (350 μM; 1 MAC) reversibly depressed EPSP amplitudes by ~60% while facilitation increased ~20%. Consistent with previous studies, these results indicate a presynaptic site of action that involves reduced excitation-release coupling. EPSPs were depressed to comparable levels by TTX (60 nM) or lowered stim, but facilitation was not changed, indicating a simple failure of axonal conduction. Similarly, partial antagonism of postsynaptic glutamate receptors with CNQX (10 μM) depressed EPSP amplitudes with no change in facilitation. However, EPSP depression by low external Ca2+ (0.8 mM) was accompanied by an increase in facilitation comparable to isoflurane. Isoflurane depression of EPSP amplitudes could also be partly reversed by high external Ca2+ (4 mM) that also decreased facilitation. Isoflurane or low Ca2+ markedly reduced the slopes of fiber volley (FV)-EPSP input-output curves, consistent with little or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope, indicating that EPSP depression resulted from FV depression. FVs were remarkably resistant to isoflurane. Somatic spike currents were unaffected by 350 μM (1 MAC) isoflurane as well. The EC50 for isoflurane depression of FVs was ~2.8 mM (12 vol. %; 8 MAC).ConclusionIsoflurane appears to depress CA1 synapses at presynaptic sites downstream from Na channels, as evident by the increased facilitation that accompanies EPSP depression. Fiber volleys did not exhibit depression by isoflurane, as has been reported for other brain regions.

Sexual differentiation of identified motor terminals inDrosophila larvae

In Drosophila, we have found that some of the motor terminals in wandering third-instar larvae are sexually differentiated. In three out of the four body-wall muscle fibers that we examined, we found female terminals that produced a larger synaptic response than their male counterparts. The single motor terminal that innervates muscle fiber 5 produces an EPSP that is 69% larger in females than in males. This is due to greater release of transmitter from female than male synaptic terminals because the amplitude of spontaneous miniature EPSPs was similar in male and female muscle fibers. This sexual difference exists throughout the third-instar: it is seen in both early (foraging) and late (wandering) third-instar larvae. The sexual differentiation appears to be neuron specific and not muscle specific because the same axon produces Is terminals on muscle fibers 2 and 4, and both terminals produce larger EPSCs in females than males. Whereas, the Ib terminals innervating muscle fibers 2 and 4 are not sexually differentiated. The differences in transmitter release are not due to differences in the size of the motor terminals. For the terminal on muscle fiber 5 and the Is terminal on muscle fiber 4, there were no differences in terminal length, the number of branches, or the number of synaptic boutons in males compared to females. These sexual differences in neuromuscular synaptic physiology may be related to male-female differences in locomotion.

Postsynaptically Synthesized Prostaglandin E2 (PGE2) Modulates Hippocampal Synaptic Transmission via a Presynaptic PGE2 EP2 Receptor

Increasing evidence suggests that cyclooxygenase-2 (COX-2) is involved in synaptic transmission and plasticity, and prostaglandin E2 (PGE2) is a key molecule in COX-2-meduated synaptic modification. However, the precise mechanisms, in particular, which subtypes of PGE2 receptors (EPs) mediate the PGE2-induced synaptic response, are not clear. Recently, we demonstrated that EPs are expressed heterogeneously in the hippocampus, and EP2/4 are mainly expressed in presynaptic terminals. Here, we report that PGE2 increased synaptic stimulus-evoked amplitudes of EPSPs in hippocampal slices and frequency of miniature EPSCs (mEPSCs) in hippocampal neurons in culture. These actions were mimicked by an EP2 agonist and attenuated by protein kinase A inhibitors. Decrease of EP2 expression through silencing the EP2 gene eliminated PGE2-induced increase of the frequency of mEPSCs. COX-2 and microsomal PGE synthase-1 (mPGES-1) and mPGES-2 are present in postsynaptic dendritic spines, because they are colocalized with PSD-95 (postsynaptic density-95), a postsynaptic marker. In addition, the frequency of mEPSCs was enhanced in neurons pretreated with interleukin-1beta or lipopolysaccharide, which elevated expression of COX-2 and mPGES-1 and produced PGE2, and this enhancement was inhibited by a COX-2 inhibitor that inhibited production of PGE2. Our results suggest that PGE2 synthesized by postsynaptically localized COX-2 functions as a retrograde messenger in hippocampal synaptic signaling via a presynaptic EP2 receptor.

The birth (and adolescence) of LTP

The birth (and adolescence) of LTP

State-Dependent Sensory Gating in Olfactory Cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Monosynaptic Connections between Pairs of Spiny Stellate Cells in Layer 4 and Pyramidal Cells in Layer 5A Indicate That Lemniscal and Paralemniscal Afferent Pathways Converge in the Infragranular Somatosensory Cortex

Monosynaptic interlaminar connections between spiny stellate cells in layer 4 (L4), the main cortical recipient layer for thalamic projections, and pyramidal cells in layer 5A (L5A), one of the main cortical output layers, were examined anatomically and functionally by paired recordings in acute brain slices. The somata of pairs forming interlaminar L4-to-L5A connections were located predominantly close to or directly under the barrel-septum wall in layer 4. Superposition of spiny stellate axon arbors and L5A pyramidal cell dendritic arbors suggested an innervation domain underneath an L4 barrel wall. Functionally, the L4-to-L5A connections were of high reliability and relatively low efficacy, with a unitary EPSP amplitude of 0.6 mV, and the connectivity was moderately high (one in seven pairs tested was connected). The EPSP amplitude was weakly depressing (paired-pulse ratio of approximately 0.8) during repetitive presynaptic action potentials at 10 Hz. The existence of monosynaptic L4-to-L5A connections indicates that the specific "lemniscal" thalamic input from the ventro-basal nucleus of the thalamus to the cortex and the more unspecific "paralemniscal" afferent thalamic projections from the posterior medial nucleus of the thalamus merge already at an initial stage of cortical signal processing. These monosynaptic connections establish a monosynaptic coupling of the input to the cortex and its output, thereby effectively bypassing the supragranular layers.

Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A) receptor chloride channels.

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 μM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABAA receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.

Reassembly and interfacing neural models registered on biological model databases.

The importance of modeling and simulation of biological process is growing for further understanding of living systems at all scales from molecular to cellular, organic, and individuals. In the field of neuroscience, there are so called platform simulators, the de-facto standard neural simulators. More than a hundred neural models are registered on the model database. These models are executable in corresponding simulation environments. But usability of the registered models is not sufficient. In order to make use of the model, the users have to identify the input, output and internal state variables and parameters of the models. The roles and units of each variable and parameter are not explicitly defined in the model files. These are suggested implicitly in the papers where the simulation results are demonstrated. In this study, we propose a novel method of reassembly and interfacing models registered on biological model database. The method was applied to the neural models registered on one of the typical biological model database, ModelDB. The results are described in detail with the hippocampal pyramidal neuron model. The model is executable in NEURON simulator environment, which demonstrates that somatic EPSP amplitude is independent of synapse location. Input and output parameters and variables were identified successfully, and the results of the simulation were recorded in the organized form with annotations.

A theoretical computer model of cellular modification associated with olfactory learning in the rat piriform cortex

Learning-associated cellular modifications were previously studied experimentally in the rat piriform cortex after operand conditioning. The results showed a 19% reduction in the level of the action potential after-hyperpolarization (AHP) in trained rats, while the spike trains indicated decreased adaptation during long depolarization. Paradoxically, this reduced AHP amplitude was associated with a level of depression in the EPSP amplitude, which was significantly higher in trained rats than in the control groups, the pseudo-trained and naive rats. Our goal in the present study is to analyze and explain through computational techniques the effect of increased EPSP depression after learning. We apply three different models to simulate the exact reduction in the AHP amplitude: (1) ‘‘ Conductance change:’’ Controlled by decreasing g kCa by 40 %. (2) ‘‘ Moving:’’ Shifting the location of the dendritic segment that exhibits active conductances, including AHP conductance, distally from the soma, while decreasing g kCa by only 15%. (3) ‘‘ Shrinkage:’’ Decreasing the length of the AHP dendritic segment, while increasing g kCa by 9%. Moving the synaptic input distally from the soma enhances EPSP depression by the AHP conductance. Hence, the learning process could be simulated by a “jump” from the control curve to any other curve, representing decreased AHP amplitude. At the same time, the enhanced EPSP depression requires an additional shift of the EPSP input to more distal locations.

Analysis of dendritic distribution of voltage-dependent channels effects on EPSP and its reciprocal inhibition in $alpha;-motoneurons: computer model

Modeling of excitation and inhibition of morphologically and physiologically characterized triceps surea motoneuron (MN 42) was executed by a NEURON simulator. The voltage-dependent channels of MN 42 were allocated on six dendrites (the rest six dendrites remained passive) according to three types of distribution functions: a step function (SF), an exponential decay (ED, highest density proximally to the soma) and exponential rise (ER, highest density distally to the soma). Maximal densities of the sodium conductance varied between 0.01 and 0.06S/cm2. The peak of the EPSP became larger as the maximal density of the voltage-dependent channels is increased. In the SF distribution, with the highest total conductance (G, Siemens), the EPSP amplitudes were greater than these in the ER and ED models. The reciprocal EPSP inhibition in the model with the SF was most efficient in comparison to the ED and ER models. EPSP peak inhibition at ED and ER are similar, despite that the total active conductance in ED is about 10 times smaller than in ER distribution. The dependency of the inhibition on the density of the active conductance in the SF and ED models is not linear. We conclude that in an “ideal neuron” the presence of proximal voltage-dependent channels may boost distally located synaptic inputs thus “normalizing” the synaptic responses.

Synaptic input from homonymous group I afferents in m. longissimus lumborum motoneurons in the L4 spinal segment in cats.

We examined the relationship between input resistance and amplitude of monosynaptic and polysynaptic EPSPs produced by electrical stimulation of group I muscle afferents innervating the m. longissimus lumborum (Long) at different levels (L1-L4) in Long motoneurons in L4 spinal segments to obtain an insight into the neuronal control of trunk muscles. In the Long motoneuron pool, the amplitude of monosynaptic EPSP was shown to have a close relationship to input resistance. Furthermore, the relation between the amplitude of polysynaptic EPSP after stimulating Long nerves at L3 and input resistance was statistically significant, but the relation between EPSP amplitude evoked by stimulation of Long at L1 or L2 and input resistance was not statistically significant. Our findings suggest a position-dependent control of motoneuron activity by group I muscle afferents. The motoneuron activities carried out by monosynaptic pathways and polysynaptic pathways from adjacent spinal segments are dependent on the intrinsic properties of motoneurons (input resistance, etc.), while the motoneuron activities carried out by polysynaptic pathways from the far spinal segments have independent intrinsic properties.

Multiple forms of long-term potentiation and long-term depression converge on a single interneuron in the leech CNS.

Long-term potentiation (LTP) of synaptic transmission was observed in two types of synapses that converge on the same postsynaptic neuron in the leech CNS. These synapses were made by identifiable sensory neurons, the mechanosensory touch (T-) and pressure (P-) cells, onto the S-cell, an interneuron critical for certain forms of learning. Changes in both the T-S and P-S synapses appear to be activity dependent because LTP was restricted to inputs that had undergone tetanization; however, properties of synaptic plasticity at the T-S and P-S connections differ considerably. At the P-S synapse, LTP was induced in the tetanized synapse but not in the nontetanized synapse tested in parallel. P-S LTP was blocked by the NMDA receptor antagonist dl-2-amino-5-phosphono-valeric acid (AP-5) or by lowering the extracellular concentration of glycine, an NMDA receptor (NMDAR) co-agonist. P-S LTP was strongly affected by the initial amplitude of the synaptic potential at the time LTP was induced. Smaller amplitude synapses (<3.5 mV) underwent robust potentiation, whereas the less common, larger amplitude synapse (>3.5 mV) depressed after tetanization. At the T-S synapse, tetanization simultaneously induced homosynaptic LTP in the tetanized input and heterosynaptic long-term depression (LTD) in the input made by a nontetanized T-cell onto the same S-cell. Interestingly, AP-5 failed to block homosynaptic LTP at the T-S synapse but did prevent heterosynaptic LTD. T-S LTP was not affected by the initial EPSP amplitude. Thus, leech neurons exhibit synaptic plasticity with properties similar to LTP and LTD found in the vertebrate nervous system.

A novel mouse brain slice preparation of the hippocampo–accumbens pathway

The nucleus accumbens (NAc) is an important component of circuitry that underlies reward related behaviors and the rewarding properties of drugs of abuse. Glutamatergic afferents to the nucleus are critical for its normal function and for behaviors related to drug addiction. An angled, sagittal mouse brain slice preparation has been designed to facilitate concurrent stimulation of two major glutamatergic afferent pathways to the nucleus accumbens. Medium spiny neurons at the medial core/shell boundary of the accumbens were depolarized by stimulation of either hippocampal or limbic cortical afferents through activation of AMPA-type glutamate receptors. High frequency but not low frequency stimulation of hippocampal afferents depolarized medium spiny neurons to a membrane potential that resembled the up state observed upon high frequency stimulation in vivo. The magnitude of the membrane depolarization was positively correlated with the amplitude of the stimulus-evoked EPSP. Concurrent stimulation of hippocampal and limbic cortical afferents at theta frequency selectively induced a long-term depression (LTD) in the magnitude of stimulus-evoked EPSPs on the hippocampal afferent only. These data suggest that this brain slice preparation can be used to study mechanisms underlying synaptic plasticity at two of the critical glutamatergic afferent synapses in the nucleus accumbens as well as characterizing potential interactions between afferents. Additionally, LTD at hippocampo–accumbens synapses can be induced at a stimulus frequency known to support reinstatement of drug seeking behavior.

Synaptic efficacy during repetitive activation of excitatory inputs in primate dorsolateral prefrontal cortex.

Neurons in the monkey dorsolateral prefrontal cortex (DLPFC) fire persistently during the delay period of working memory tasks. To determine how repetitive firing affects the efficacy of synaptic inputs to DLPFC layer 3 neurons, we examined the effects of repetitive presynaptic stimulation on the amplitude and temporal summation of EPSPs. Recordings were obtained in monkey DLPFC brain slices from regular spiking (RS) pyramidal cells and two types of interneurons, fast spiking (FS) and adapting non-pyramidal (ANP) cells. Repetitive stimulation of presynaptic axons in layer 3 caused EPSP depression in RS and FS neurons, but EPSP facilitation in ANP cells. A shorter EPSP duration produced weaker temporal summation in FS neurons compared to the other cell classes. Thus, due to the combined effects of dynamic changes in EPSP amplitude and differences in temporal summation, the effect of a presynaptic spike train differed according to the postsynaptic cell class. Similar results were obtained when recording unitary EPSPs evoked in connected pairs of presynaptic RS pyramidal cells and postsynaptic RS, FS or ANP neurons. In addition, similar differences in the efficacy of sustained inputs among cell classes were observed when delay-related firing was reproduced in vitro by stimulating inputs with the timing of spike trains recorded from the DLPFC of monkeys performing a delayed-response task. We suggest that the transition from baseline firing rates to higher frequency delay-related firing may lead to the differential activation of distinct cell populations, with corresponding significant effects on the patterns of activity in local prefrontal circuits.

Analysis of dendritic distribution of voltage-dependent channels effects on EPSP and its reciprocal inhibition in α-motoneurons: computer model

Modeling of excitation and inhibition of morphologically and physiologically characterized triceps surea motoneuron (MN 42) was executed by a NEURON simulator. The voltage-dependent channels of MN 42 were allocated on six dendrites (the rest six dendrites remained passive) according to three types of distribution functions: a step function (SF), an exponential decay (ED, highest density proximally to the soma) and exponential rise (ER, highest density distally to the soma). Maximal densities of the sodium conductance varied between 0.01 and 0.06 S/cm 2 . The peak of the EPSP became larger as the maximal density of the voltage-dependent channels is increased. In the SF distribution, with the highest total conductance ( G, Siemens), the EPSP amplitudes were greater than these in the ER and ED models. The reciprocal EPSP inhibition in the model with the SF was most efficient in comparison to the ED and ER models. EPSP peak inhibition at ED and ER are similar, despite that the total active conductance in ED is about 10 times smaller than in ER distribution. The dependency of the inhibition on the density of the active conductance in the SF and ED models is not linear. We conclude that in an “ideal neuron” the presence of proximal voltage-dependent channels may boost distally located synaptic inputs thus “normalizing” the synaptic responses.

The nitric oxide-guanylyl cyclase signaling pathway modulates membrane activity States and electrophysiological properties of striatal medium spiny neurons recorded in vivo.

Nitric oxide (NO)-releasing interneurons are believed to regulate the activity of striatal medium spiny neurons (MSNs) that contain the NO effector enzyme guanylyl cyclase (GC). The involvement of NO-GC signaling in modulating steady-state membrane activity of striatal MSNs was examined using in vivo intracellular recordings in rats. Intrastriatal infusion of a neuronal NO synthase inhibitor or a NO scavenger via reverse microdialysis consistently decreased the amplitude of spontaneously occurring depolarized plateau potentials (up events). Intrastriatal infusion of a NO scavenger also decreased the amplitude of EPSPs evoked during electrical stimulation of the orbital prefrontal cortex. The effect of the NO scavenger on spontaneous up events was partially reversed by coperfusion with a cell-permeable cGMP analog. Intracellular injection of MSNs with a soluble GC inhibitor resulted in large decreases in the following: (1) spontaneous up-event amplitude, (2) responsiveness to depolarizing current, (3) action potential amplitude, and (4) input resistance. These effects were partially reversed by coinjection of cGMP. Conversely, intracellular injection of a phosphodiesterase inhibitor increased MSN neuron membrane excitability. These results indicate that, in the intact animal, the NO signaling pathway exerts a powerful tonic modulatory influence over the membrane activity of striatal MSNs via the activation of GC and stimulation of cGMP production.

Changes in the Properties of Glutamatergic Synapses in the Medial Prefrontal Cortex and Nucl. Accumbens in Rats with Behavioral Depression

In experiments on surviving rat forebrain slices, we studied the characteristics of glutamatergic synaptic transmission in the medial prefrontal cortex (MPFC) and nucl. accumbens. It was found that in rats with behavioral depression induced by zoosocial isolation (72 h), the mean amplitude of field EPSP (fEPSP) in the MPFC demonstrated no significant alterations. At the same time, the developments of rhythmic stimulation-caused long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission were suppressed, as compared with the control. In the nucl. accumbens of rats with behavioral depression, the mean fEPSP amplitude increased by nearly 25%, whereas rhythmic stimulation-induced LTD of transmission through synaptic connections between the cortex and nucl. accumbens weakened. Changes in the relay and plastic properties of glutamatergic synapses typical of behavioral depression were reproduced under conditions of chronic (for 3 days) i.p. injections of 1 mg/kg dexamethasone into the experimental animals. The influences exerted on brain slices in vitro by a synthetic glucocorticoid, dexamethasone, and a mineralocorticoid, deoxycorticosterone acetate, applied over 2 h in concentrations of 100 nM, did not significantly affect glutamatergic synaptic transmission in the MPFC and nucl. accumbens. In brain slices from animals with behavioral depression or from those subjected to chronic injection of dexamethasone, we observed a reduction of the modulatory effect of dexamethasone and a nonselective agonist of dopamine receptors, apomorphine hydrochloride, on glutamatergic synaptic transmission in the MPFC and nucl. accumbens. This is considered an indirect reflection of a decrease in the efficiency (down-regulation) of glucocorticoid and dopamine receptors in neurons of the brain structures under study. It is hypothesized that changes in the main properties of glutamatergic synapses in the forebrain structures (MPFC and nucl. accumbens), which were observed under conditions of behavioral depression, are determined by both direct effects of glucocorticoids on cortical and mesolimbic neurons and indirect effects mediated by the cerebral dopaminergic system.

Nonlinear Integration of Sensory Responses in the Rat Barrel Cortex: An Intracellular StudyIn Vivo

To study integration of converging sensory inputs on single cortical neurons, we performed intracellular recordings in vivo in the barrel cortex of the barbiturate-anesthetized rat. We deflected the principal whisker (PW) for each cell either alone or preceded (at 20, 50, and 100 msec) by the deflection of a small number of remote whiskers (RWs) far from the PW. The synaptic responses to both the PW and the RW were similar qualitatively and consisted of excitation followed by inhibition that comprised an early and a late component. The RW response was of smaller amplitude and more often subthreshold for action potential generation. The main effect of the RW deflection was a suppression of the subsequent response to the PW that was most pronounced at the 20 msec interval and decreased progressively at the 50 and 100 msec intervals. Suppression of the spike output of the cell was not caused by hyperpolarization (subtractive inhibition) but by a reduction in the EPSP amplitude (divisive inhibition), resulting in a highly sublinear summation of the two responses. The small decrease in input resistance caused by the RW responses is not consistent with synaptic shunting as the main cause of the reduction of the EPSP amplitude. Instead, our results suggest that suppression results from a decrease in the amount of synaptic input triggered by the PW, particularly the early excitation. We suggest that this process involves a reduction in reverberant granular cell excitation that is induced by PW deflection.

Spike Width Reduction Modifies the Dynamics of Short-Term Depression at a Central Synapse in the Locust

Short-term synaptic depression is an important component of computation within neural networks, but little is known of its contribution to information processing during synaptically generated spike trains. We analyzed short-term synaptic depression at a synapse between two identified motoneurons innervating the hind leg of the locust: the FETi-FlTi synapse (fast extensor tibiae-flexor tibiae). Brief electrical stimulation of a single hind leg proprioceptor, the lump receptor (LR), led to prolonged sequences of spikes in FETi, similar in number and frequency to those during natural kicking movements. Depression at the FETi-FlTi synapse during LR-evoked spike bursts was compared quantitatively to that during antidromic spike trains evoked by electrical stimulation of FETi in the extensor tibiae muscle, and by modeling. The magnitude of the short-term depression was significantly greater during LR-evoked spike trains. On the basis of the model parameters required to fit the depression, the FETi-FlTi synapse is predominantly used for transmitting the timing of the onset of FETi spiking rather than its spike rate. During LR-evoked spike trains, there was a rapid reduction in presynaptic spike width that did not occur during antidromic spike trains under physiological calcium concentrations. This produced a concomitant reduction in the amplitude of the FlTi EPSP, suggesting that it contributed to the differences between the two stimulation regimes. Differences in the short-term depression between synaptically evoked and antidromic spike trains emphasize that the properties of synaptic information transfer are dependent on the in vivo conditions at the synapse and may not be reproduced by in vitro spike trains.

Pyramidal cell communication within local networks in layer 2/3 of rat neocortex.

The extent to which neocortical pyramidal cells function as a local network is determined by the strength and probability of their connections. By mapping connections between pyramidal cells we show here that in a local network of about 600 pyramidal cells located within a cylindrical volume of 200 microm x 200 microm of neocortical layer 2/3, an individual pyramidal cell receives synaptic inputs from about 30 other pyramidal neurons, with the majority of EPSP amplitudes in the 0.2-1.0 mV range. The probability of connection decreased from 0.09 to 0.01 with intercell distance (over the range 25-200 microm). Within the same volume, local interneuron (fast-spiking non-accommodating interneuron, FS)-pyramidal cell connections were about 10 times more numerous, with the majority of connections being reciprocal. The probability of excitatory and inhibitory connections between pyramidal cells and FS interneurons decreased only slightly with distance, being in the range 0.5-0.75. Pyramidal cells in the local network received strong synaptic input during stimulation of afferent fibres in layers 1 and 6. Minimal-like stimulation of layer 1 or layer 6 inputs simultaneously induced postsynaptic potentials in connected pyramidal cells as well as in pyramidal-FS cell pairs. These inputs readily induced firing of pyramidal cells, although synaptically connected cells displayed different firing patterns. Unitary EPSPs in pyramidal-pyramidal cell pairs did not detectably alter cell firing. FS interneurons fire simultaneously with pyramidal cells. In pyramidal-FS cell pairs, both unitary EPSPs and IPSPs efficiently modulated cell firing patterns. We suggest that computation in the local network may proceed not only by direct pyramidal-pyramidal cell communication but also via local interneurons. With such a high degree of connectivity with surrounding pyramidal cells, local interneurons are ideally poised to both coordinate and expand the local pyramidal cell network via pyramidal-interneuron-pyramidal communication.