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PubMed1998

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons.

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons. J. Neurophysiol. 80: 3284-3296, 1998. When low-frequency tetanization of the mesencephalic locomotor region (MLR) produce fictive locomotion in unanesthetized, decerebrate cats, each MLR stimulus produces a distinctive cord dorsum potential (CDP) and oligosynaptic excitatory postsynaptic potentials (EPSPs) in many lumbosacral motoneurons. The average segmental latency from the initial CDP wave [mean delay from stimulus: 4.3 +/- 0.9 (SD) ms] to the onset of detectable MLR EPSPs was 1.6 +/- 0.4 ms, suggesting a disynaptic segmental connection. In gastrocnemius/soleus, flexor hallucis longus, flexor digitorum longus, tibialis anterior, and posterior biceps-semitendinosus motoneurons (35/38 cells), MLR EPSPs either appeared or were enhanced during the phase of fictive stepping in which the target motoneurons were depolarized and the motor pool was active (the phase), with parallel changes between EPSP amplitudes and membrane depolarization. In contrast, MLR stimulation produced small (1/10) or no EPSPs in extensor digitorum longus (EDL) motoneurons, with no phase enhancement (4/10) or oligosynaptic inhibitory postsynaptic potentials during the phase (5/10). Eight of 10 flexor digitorum longus (FDL) cells exhibited membrane depolarization in the early flexion phase of fictive stepping, and five of these showed parallel enhancement of disynaptic MLR EPSPs during early flexion. Three cases were studied when the FDL motor pool exhibited exclusively extensor phase firing. In these cases, the disynaptic MLR EPSPs were enhanced only during the extensor phase, accompanied by membrane depolarizations. We conclude that the last-order interneurons that produce disynaptic MLR EPSPs may well participate in producing the depolarizing locomotor drive potentials (LDPs) found in hindlimb motoneurons during fictive locomotion. However, the absence of linkage between MLR EPSP enhancement and LDP depolarizations in EDL motoneurons suggests that other types of excitatory interneurons also must be involved at least in some motor pools. We compared these patterns with the modulation of disynaptic EPSPs produced in FDL cells by stimulation of the medial longitudinal fasciculus (MLF). In all seven FDL motoneurons tested, disynaptic MLF EPSPs appeared only during the extension phase, regardless of when the FDL motoneurons were active. The fact that the modulation patterns of MLR and MLF disynaptic EPSPs is different in FDL motoneurons indicates that the two pathways do not converge on common last-order interneurons to that motor pool.

Animals↗
PubMed2001

Bipolar cells contribute to nonlinear spatial summation in the brisk-transient (Y) ganglion cell in mammalian retina.

The receptive field of the Y-ganglion cell comprises two excitatory mechanisms: one integrates linearly over a narrow field, and the other integrates nonlinearly over a wide field. The linear mechanism has been attributed to input from bipolar cells, and the nonlinear mechanism has been attributed to input from a class of amacrine cells whose nonlinear "subunits" extend across the linear receptive field and beyond. However, the central component of the nonlinear mechanism could in theory be driven by bipolar input if that input were rectified. Recording intracellularly from the Y-cell in guinea pig retina, we blocked the peripheral component of the nonlinear mechanism with tetrodotoxin and found the remaining nonlinear receptive field to be precisely co-spatial with the central component of the linear receptive field. Both linear and nonlinear mechanisms were caused by an excitatory postsynaptic potential that reversed near 0 mV. The nonlinear mechanism depended neither on acetylcholine nor on feedback involving GABA or glycine. Thus the central components of the ganglion cell's linear and nonlinear mechanisms are apparently driven by synapses from the same rectifying bipolar cell.

Action Potentials↗
PubMed1998

Mechanisms of excitatory synaptic transmission in the enteric nervous system.

The enteric nervous system can control gastrointestinal function independent of direct connections with the central nervous system. Enteric nerves can perform this task as there are multiple mechanisms of excitatory neurotransmission in enteric ganglia. There are two broad types of excitatory synaptic transmission, fast and slow excitatory synaptic responses. Fast excitatory postsynaptic potentials (fEPSPs) are recorded from "S" type neurons and some AH type neurons. S neurons are interneurons and motorneurons while AH neurons are intrinsic sensory neurons. Slow excitatory postsynaptic potentials (sEPSPs) can be recorded from some S neurons and also from AH type neurons. The fEPSPs recorded from S neurons and mediated largely by acetylcholine acting at nicotinic cholinergic receptors (nAChRs). However, ATP acting at P2X purine receptors contributes to the fEPSP in many S neurons. The fEPSPs recorded from AH neurons are also mediated largely by nAChRs but glutamate acting at AMPA receptors contributes to fEPSPs in some AH neurons. The sEPSPs in AH neurons are mediated by one or more neuropeptides and 5-hydroxytryptamine. The sEPSPs in AH neurons are due to inhibition of two types of resting potassium channels and activation of a chloride channel or a nonspecific cation channel. The multiple mechanisms of excitatory synaptic transmission in the enteric nervous system contribute to its capacity to regulate complex gastrointestinal functions.

Animals↗
PubMed2003

Physiology of human cortical neurons adjacent to cavernous malformations and tumors.

PURPOSE: Focal neocortical seizures can be associated with a number of specific pathologies including supratentorial tumors and cavernous malformations (CMs), both of which are highly epileptogenic. METHODS: To begin to address the question of whether these lesions have different mechanisms of epileptogenesis, we used intracellular recordings from neurons adjacent to intracerebral neoplasms and cerebral CMs. Developmental anomalies were not included in this study. RESULTS: Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex spontaneous synaptic events than did neurons neighboring neoplastic substrates (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p < 0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast, in tissue adjacent to tumors, low-amplitude (<3 mV) spontaneous excitatory activity predominated. Neurons neighboring CMs also exhibited more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these cells, versus 32% of cells from the tumor group; p < 0.05. In studies using hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue adjacent to CMs. CONCLUSIONS: These data suggest that CMs may induce seizure activity via a different pathophysiologic mechanism(s) than glial tumors.

Adolescent↗
PubMed2001

Kindling induces transient NMDA receptor-mediated facilitation of high-frequency input in the rat dentate gyrus.

To elucidate the gating mechanism of the epileptic dentate gyrus on seizure-like input, we investigated dentate gyrus field potentials and granule cell excitatory postsynaptic potentials (EPSPs) following high-frequency stimulation (10-100 Hz) of the lateral perforant path in an experimental model of temporal lobe epilepsy (i.e., kindled rats). Although control slices showed steady EPSP depression at frequencies greater than 20 Hz, slices taken from animals 48 h after the last seizure presented pronounced EPSP facilitation at 50 and 100 Hz, followed by steady depression. However, 28 days after kindling, the EPSP facilitation was no longer detectable. Using the specific N-methyl-D-aspartate (NMDA) and RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA) receptor antagonists 2-amino-5-phosphonovaleric acid and SYM 2206, we examined the time course of alterations in glutamate receptor-dependent synaptic currents that parallel transient EPSP facilitation. Forty-eight hours after kindling, the fractional AMPA and NMDA receptor-mediated excitatory postsynaptic current (EPSC) components shifted dramatically in favor of the NMDA receptor-mediated response. Four weeks after kindling, however, AMPA and NMDA receptor-mediated EPSCs reverted to control-like values. Although the granule cells of the dentate gyrus contain mRNA-encoding kainate receptors, neither single nor repetitive perforant path stimuli evoked kainate receptor-mediated EPSCs in control or in kindled rats. The enhanced excitability of the kindled dentate gyrus 48 h after the last seizure, as well as the breakdown of its gating function, appear to result from transiently enhanced NMDA receptor activation that provides significantly slower EPSC kinetics than those observed in control slices and in slices from kindled animals with a 28-day seizure-free interval. Therefore, NMDA receptors seem to play a critical role in the acute throughput of seizure activity and in the induction of the kindled state but not in the persistence of enhanced seizure susceptibility.

2-Amino-5-phosphonovalerate↗
PubMed2003

Muscle afferent inputs from the hand activate human cerebellum sequentially through parallel and climbing fiber systems.

OBJECTIVE: Spatio-temporal response characteristics of the human cerebellum to median nerve stimulation (MNS) were studied with the use of a whole-head magnetoencephalographic (MEG) system covering the cerebellum and upper cervical spine. METHODS: Neuromagnetic responses from the cerebellum were recorded following electric stimulation of the right median nerve in 12 subjects. In 6 out of 12 subjects, the responses to the left median nerve and to the right index or middle finger stimulation were also recorded. RESULTS: The medial part of the cerebellum (spinocerebellum) was activated by MNS. In contrast, there were no responses from the cerebellum to the finger stimulation, suggesting that muscle afferent inputs are the source of cerebellar activation for MNS. The cerebellar responses consisted of 3 or 4 components of alternating polarity within 90 ms post-stimulus: the current direction for the first component was from the depth to the surface of the anterior lobe. CONCLUSIONS: From the timing and current direction, we speculate that the 4 components reflect, respectively, (1) excitatory postsynaptic potentials (EPSPs) of granule cells, (2) Purkinje cell EPSPs at the distal dendrites driven by parallel fibers, (3) Purkinje cell EPSPs at the soma and the proximal dendrites mediated by climbing fibers and (4) second Purkinje cell EPSPs at the distal dendrites driven by parallel fibers. SIGNIFICANCE: We first visualized serial activation of the human spinocerebellum following MNS noninvasively with MEG.

Adult↗
PubMed1998

(+)-MCPG blocks induction of LTP in CA1 of rat hippocampus via agonist action at an mGluR group II receptor.

We investigated the effect of metabotropic glutamate receptor (mGluR) ligands on the induction of long-term potentiation (LTP) of field excitatory postsynaptic potentials (EPSPs) in CA1 of rat hippocampus, in particular the manner by which the nonsubtype selective mGluR ligand alpha-methyl-4-carboxyphenylglycine [(+)-MCPG] blocks LTP induction. Normalized control LTP was blocked by (+)-MCPG (250 microM), but not by the mGluRI selective antagonist (S)-4-carboxyphenylglycine (4-CPG), the mGluRII selective antagonist 1/(2S,3S, 4S)-2-methyl-2-(carboxycyclopropyl) glycine (MCCG), or the mGluRIII antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid/alpha-methyl (MAP4). In contrast the mGluRII agonist ((1S, 3S)-1-aminocyclopentante-1,3-dicarboxylic acid -(1S,3S)-ACPD-; 10 or 25 microM) completely and consistently blocked LTP. The block of LTP by both (1S,3S)-ACPD and (+)-MCPG could be prevented by preincubation with the mGluRII antagonist MCCG. These studies demonstrate that (+)-MCPG blocks LTP induction through an agonist action at an mGluRII receptor and not through a nonselective antagonist action.

Amino Acids, Dicarboxylic↗
PubMed2002

Boosting of neuronal firing evoked with asynchronous and synchronous inputs to the dendrite.

Dendritic conductances have previously been shown to boost excitatory postsynaptic potentials (EPSPs). To determine whether this boosting translates to an increase in the efficacy for evoking action potentials, we injected barrages of EPSPs that simulate the inputs generated by a population of presynaptic cells into either the dendrite or the soma of pyramidal neurons in vitro. Although the individual dendritic and somatic EPSPs were identical, barrages delivered to the dendrite generated much higher firing rates. Boosting occurred when the simulated cells fired asynchronously and synchronously. This Na+-mediated boosting, which was manifested during repetitive firing, may compensate functionally for electrotonic attenuation of EPSPs.

Action Potentials↗
PubMed1988

AF-DX 116: a selective antagonist of the slow inhibitory postsynaptic potential and methacholine-induced hyperpolarization in superior cervical ganglion of the rabbit.

AF-DX 116 [11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiaze pine-6-one], a muscarinic receptor antagonist that divides the M2-type muscarinic receptor into additional functional classes, modified muscarinic responses recorded from the superior cervical ganglion of the rabbit with sucrose or air gap techniques. Incubation of ganglia with AF-DX 116 suppressed the amplitude of the slow-inhibitory postsynaptic potential (s-IPSP) in a concentration-dependent and highly specific manner. At concentrations which reduced the amplitude of the s-IPSP by 80 to 90%, there was no significant reduction of the amplitudes of the muscarinic slow-excitatory postsynaptic potential or the nicotinic fast-excitatory postsynaptic potential. In addition, superfusion of ganglia with AF-DX 116 resulted in the concentration-dependent suppression of ganglionic hyperpolarization induced by methacholine without suppression of methacholine-induced depolarization. Ganglionic hyperpolarization that was produced by norepinephrine was unaffected by AF-DX 116. Increasing the level of acetylcholine available for interaction with muscarinic receptors by increasing the number of stimulus volleys that were applied to the preganglionic nerve resulted in a parallel shift, to the right, of the concentration-response curve for suppression of the s-IPSP by AF-DX 116. Similarly, incubation of ganglia with the specific antiacetylcholinesterase, BW 284 (1-5-bis[4-allyl dimethylammonium phenyl]pentan-3 one dibromide), increased the concentration of AF-DX 116 that was required to produce a comparable suppression of the s-IPSP. These results indicate that the s-IPSP in mammalian superior cervical ganglion involves an action of acetylcholine at the M2 type receptor that is preferentially blocked by AF-DX 116.

Animals↗
PubMed2004

Effects of cortical stimulation on auditory-responsive thalamic neurones in anaesthetized guinea pigs.

In the present study, we investigated neuronal responses to acoustic stimuli and cortical stimulation in the medial geniculate body (MGB) through in vivo intracellular recordings in anaesthetized guinea pigs. Of the 54 neurones examined with acoustic stimuli, 36 showed excitatory postsynaptic potential (EPSP) responses and 19 showed inhibitory postsynaptic potential (IPSP) responses to acoustic stimuli. Of the 36 EPSP neurones examined with corticofugal modulation, 29 received corticofugal depolarization, 3 corticofugal inhibition, and 4 showed no effect. Of the 19 IPSP neurones, 17 received corticofugal inhibition and 2 were not affected. The mean amplitude of the EPSPs evoked by acoustic stimuli was similar to that evoked by the electrical cortical stimulation (9.19 +/- 5.55 mV versus 9.22 +/- 5.16 mV). There was a significant correlation between the parameters of the EPSPs evoked by an acoustic stimulus and those evoked by cortical stimulation. The mean amplitude of the IPSP evoked by electrical cortical stimulation was significantly greater than that evoked by acoustic stimuli (11.6 +/- 3.8 mV versus 9.1 +/- 3.7 ms, P < 0.05). Seven auditory EPSP and 7 IPSP neurones were examined with corticofugal modulation and labelled with Neurobiotin. Of the 7 EPSP neurones, 5 showed excitatory responses to cortical stimulation and 2 demonstrated no effects. Four of the 5 neurones that received corticofugal depolarization were located in the lemniscal MGB and 1 in the non-lemniscal MGB; of the remaining 2, 1 was located in the lemniscal and the other in the non-lemniscal MGB. Of the 7 IPSP neurones, 1 received an excitatory corticofugal input followed by an inhibitory input and 4 received only an inhibitory corticofugal input, while the remainder demonstrated no corticofugal effects. All 7 neurones were located in the non-lemniscal MGB. The result that both ascending and descending inputs caused similarly shaped EPSPs reflects a neuronal endogenous characteristic irrespective of the physical locations of the synapses. The IPSP responses to both acoustic stimuli and electrical cortical stimulation are likely to be caused by feedback from the thalamic reticular nucleus.

Acoustic Stimulation↗
PubMed2003

EEG oscillations at 600 Hz are macroscopic markers for cortical spike bursts.

The human electroencephalogram (EEG) is generated predominantly by synchronised cortical excitatory postsynaptic potentials oscillating at frequencies <100 Hz. Unusually, EEG responses to electrical nerve stimulation contain brief bursts of high-frequency (600 Hz) wavelets. Here we show, in awake monkeys, that a subset of primary somatosensory cortex single units consistently fires both bursts and single spikes phase-locked to EEG wavelets. Spike bursts were also evoked by tactile stimuli, proving that this is a natural response mode. EEG wavelets at 600 Hz may therefore permit non-invasive assessment of population spike timing in human cortex.

Animals↗
PubMed1998

Strength and orientation tuning of the thalamic input to simple cells revealed by electrically evoked cortical suppression.

Is thalamic input to the visual cortex strong and well tuned for orientation, as predicted by Hubel and Wiesel's (1962) model of orientation selectivity in simple cells? We directly measured the size of the thalamic input to single simple cells intracellularly by combining electrical stimulation of the cortex with a briefly flashed visual stimulus. In nearby cells, the electrical stimulation evoked a long-lasting inhibition that prevented them from firing in response to the visual stimulus. The visually evoked excitatory postsynaptic potentials (EPSPs) recorded during the period of cortical suppression, therefore, reflected largely the thalamic input. In 16 neurons that received monosynaptic input from the thalamus, cortical suppression left 46% of normal visual response on average (12%-86% in range). In those cells tested, this remaining visual response was as well tuned for orientation as the normal response to the visual stimulus alone. We conclude that the thalamic input to cortical simple cells with monosynaptic input from the thalamus is strong and well tuned in orientation, and that the intracortical input does not appear to sharpen orientation tuning in these cells.

Animals↗
PubMed1998

Dendritic voltage and calcium-gated channels amplify the variability of postsynaptic responses in a Purkinje cell model.

The dendrites of most neurons express several types of voltage and Ca2+-gated channels. These ionic channels can be activated by subthreshold synaptic input, but the functional role of such activations in vivo is unclear. The interaction between dendritic channels and synaptic background input as it occurs in vivo was studied in a realistic computer model of a cerebellar Purkinje cell. It previously was shown using this model that dendritic Ca2+ channels amplify the somatic response to synchronous excitatory inputs. In this study, it is shown that dendritic ion channels also increased the somatic membrane potential fluctuations generated by the background input. This amplification caused a highly variable somatic excitatory postsynaptic potential (EPSP) in response to a synchronous excitatory input. The variability scaled with the size of the response in the model with excitable dendrite, resulting in an almost constant coefficient of variation, whereas in a passive model the membrane potential fluctuations simply added onto the EPSP. Although the EPSP amplitude in the active dendrite model was quite variable for different patterns of background input, it was insensitive to changes in the timing of the synchronous input by a few milliseconds. This effect was explained by slow changes in dendritic excitability. This excitability was determined by how the background input affected the dendritic membrane potentials in the preceding 10-20 ms, causing changes in activation of voltage and Ca2+-gated channels. The most important model variables determining the excitability at the time of a synchronous input were the Ca2+-activation of K+ channels and the inhibitory synaptic conductance, although many other model variables could be influential for particular background patterns. Experimental evidence for the amplification of postsynaptic variability by active dendrites is discussed. The amplification of the variability of EPSPs has important functional consequences in general and for cerebellar Purkinje cells specifically. Subthreshold, background input has a much larger effect on the responses to coherent input of neurons with active dendrites compared with passive dendrites because it can change the effective threshold for firing. This gives neurons with dendritic calcium channels an increased information processing capacity and provides the Purkinje cell with a gating function.

Action Potentials↗
PubMed1995

In vitro study of afferent synaptic transmission in the rostral gustatory zone of the rat nucleus of the solitary tract.

The synaptic responses of rostral nucleus of the solitary tract (rNST) neurons to electrical stimulation of the solitary tract (ST) fibers were investigated using whole-cell recordings in brain slices of adult rat medulla. Most neurons of the rNST (47%) responded to stimulation of the ST with excitatory postsynaptic potentials (EPSPs), 28% responded with mixed excitatory and inhibitory postsynaptic potentials (PSPs) and 25% responded with inhibitory postsynaptic potentials (IPSPs). The estimated reversal potentials for the EPSPs (EEPSP) was -7 mV and for the IPSPs (EIPSP) was -69 mV. The glutamate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) acting at the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor, either reduced or blocked all EPSPs tested. D-2-Amino-5-phosphonovalerate (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the amplitude of the EPSPs. These results suggest that glutamate is released following stimulation of afferent fibers in the ST and acts on both AMPA/kainate and NMDA glutamate receptors. The IPSPs result from release of gamma-aminobutyric acid (GABA) since superfusion of the GABAA receptor antagonist, bicuculline reversibly blocked the IPSPs. The GABAB receptor antagonist, phaclofen, also reduced the IPSP components in some neurons, indicating that both GABAA and GABAB receptors are involved in inhibitory transmission in the rNST. When the morphology of the recorded neurons was examined by filling the neurons with biocytin and reconstructing the neurons, each morphological type of rNST neuron responded with excitatory and inhibitory PSPs following stimulation of the ST.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2006

Serotonin-immunoreactive CPT interneurons in Hermissenda: identification of sensory input and motor projections.

Serotonin immunoreactive (5-HT-IR) neurons identified as cerebropleural ganglion triplets (CPTs) in Hermissenda may be homologues of 5-HT-IR neurons identified in other opisthobranch molluscs. In studies of isolated nervous systems and semi-intact preparations we used a combination of immunohistochemical techniques and fluorescent labeling with Lucifer yellow to identify 5-HT-IR CPT neurons after investigating sensory inputs and motor neuron projections. Here we show that identified 5-HT-IR CPT interneurons receive sensory input from mechanoreceptors and photoreceptors. In semi-intact preparations with intact pedal nerves P1 and P2, cutaneous stimulation of the middle or tail regions of the foot with calibrated von Frey hairs elicited spikes recorded from identified CPT interneurons. Illumination of the eyes evoked a small complex excitatory postsynaptic potential (EPSP) and resulted in a modest increase in the spike discharge of CPT interneurons. Immunostaining of Lucifer yellow-labeled neurons revealed that CPT interneurons projected an axonal process to the contralateral pedal ganglion. Depolarization of CPT interneurons with extrinsic current evoked EPSPs and spikes recorded from identified VP2 pedal neurons, motor neurons previously shown to elicit movement of the anterior foot. Extrinsic current stimulation of CPT interneurons in semi-intact preparations evoked movement of the anterior foot but did not facilitate ciliary activity or evoke PSPs recorded in identified VP1 ciliary motor neurons. Our results show that CPT neurons are polysensory interneurons that contribute to reflexive foot contractions in Hermissenda.

Action Potentials↗
PubMed1999

N-methyl-D-aspartate receptor antagonists are less effective in blocking long-term potentiation at apical than basal dendrites in hippocampal CA1 of awake rats.

Long-term potentiation (LTP) of field excitatory postsynaptic potentials (fEPSPs) at the apical or basal dendrites of CA1 pyramidal cells was induced by stimulation with a 1-s train of 200-Hz pulses in awake rats, with or without the presence of various doses of an N-methyl-D-aspartate (NMDA) receptor antagonist. Apical LTP was blocked by an intracerebroventricular (i.c.v.) dose of 40 microg D-2-amino-5-phosphonopentanoic acid (D-AP5) or 20 mg/kg i.p. D-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP-40116), whereas basal LTP was blocked by half the dose of D-AP5 or CGP-40116. The noncompetitive antagonist MK-801 (< or =1 mg/kg i.p.) had no significant effect on apical LTP. Apical LTP was not blocked by i.c.v. nifedipine. The effect of an NMDA receptor antagonist alone on apical and basal fEPSPs was also evaluated, to assess the net effect of the NMDA receptor antagonist in blocking LTP. MK-801 (0.5-1 mg/kg i.p.) or CGP-40116 (10-20 mg/kg i.p.) but not D-AP5 suppressed apical fEPSPs for several hours and confounded the expression of apical LTP during this time. We concluded that hippocampal LTP at different synapses has different sensitivity to NMDA receptor antagonists and that a general blockade of hippocampal NMDA receptor functions cannot be inferred by a single hippocampal LTP measure.

2-Amino-5-phosphonovalerate↗
PubMed2002

Removal of GABAergic inhibition alters subthreshold input in neurons in forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) after digit stimulation.

Our objective was to test the hypothesis that suppression of GABAergic inhibition results in an enhancement of responses to stimulation of the surround receptive field. Neurons in the forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) receive short latency suprathreshold input from a principal location on the forepaw and longer latency subthreshold input from surrounding forepaw skin regions. Input from principal and surround receptive field sites was examined before, during, and after administration of the GABA(A) receptor blocker bicuculline methiodide (BMI) (in 165 mM NaCl at pH 3.3-3.5). In vivo extracellular recording was used to first identify the location of the glabrous forepaw digit representation within the FBS. In vivo intracellular recording and labeling techniques were then used to impale single FBS neurons in layer IV as well as neurons in layers III and V, determine the receptive field of the cell, and fill the cell with biocytin for subsequent morphological identification. The intracellular recording electrode was fastened with dental wax to a double-barrel pipette for BMI iontophoresis and current balance. A stimulating probe, placed on the glabrous forepaw skin surface, was used to identify principal and surround components of the receptive field. Once a cell was impaled and a stable recording was obtained, a stimulating probe was placed at a selected site within the surround receptive field. Single-pulse stimulation (1 Hz) was then delivered through the skin probe and the percentage of spikes occurring in 1-min intervals before BMI onset was used as a baseline measure. BMI was then iontophoresed while the periphery was simultaneously stimulated, and spike percentage measured during and after BMI ejection was compared with the pre-BMI baseline. The major findings are: (1) suppression of GABAergic inhibition enhanced evoked responses to firing level from sites in surround receptive fields in 65% of the cells ( n=17); (2) evoked responses were rapidly elevated (within 1 min) to suprathreshold firing in the presence of BMI in 31% of the cells; (3) GABAergic inhibition was reversible [suprathreshold spiking gradually reversed to subthreshold excitatory postsynaptic potentials (EPSPs) in 45% of the cells tested]; (4) BMI altered the stimulus-evoked and non-stimulus-evoked firing pattern in SI neurons from single spikes to burst patterns in all tested cells; and (5) iontophoresis of NaCl (165 mM) without BMI was ineffective in altering evoked responses in control cells ( n=4). The present findings support the notion that subthreshold input from surround receptive fields is one possible mechanism for rapid cortical reorganization in barrel cortex and that GABAergic inhibition may regulate its expression. Possible corticocortical and thalamocortical substrates for subthreshold input to reach barrel neurons are discussed.

Action Potentials↗
PubMed2002

Contribution of T-type VDCC to TEA-induced long-term synaptic modification in hippocampal CA1 and dentate gyrus.

We have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long-term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long-term synaptic modification in CA1 and DG results from different levels of TEA-elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T-type voltage-dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L-type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T-type and L-type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA-sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T-type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L-type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T-type VDCCs, rather than L-type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA-LTP in CA1 depends primarily on T-type, rather than L-type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T-type VDCCs in granule cell membranes.

Animals↗