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At least 991 records · Page 55Linked to original sources
PubMed2005

Coupled networks of parvalbumin-immunoreactive interneurons in the rat basolateral amygdala.

Recent studies indicate that the basolateral amygdala exhibits fast rhythmic oscillations during emotional arousal, but the neuronal mechanisms underlying this activity are not known. Similar oscillations in the cerebral cortex are generated by a network of parvalbumin (PV)-immunoreactive interneurons interconnected by chemical synapses and dendritic gap junctions. The present immunoelectron microscopic study revealed that the basolateral amygdalar nucleus (BLa) contains a network of parvalbumin-immunoreactive (PV+) interneurons interconnected by chemical synapses, dendritic gap junctions, and axonal gap junctions. Twenty percent of synapses onto PV+ neurons were formed by PV+ axon terminals. All of these PV+ synapses were symmetrical. PV+ perikarya exhibited the greatest incidence of PV+ synapses (30%), with lower percentages associated with PV+ dendrites (15%) and spines (25%). These synapses comprised half of all symmetrical synapses formed with PV+ cells. A total of 18 dendrodendritic gap junctions between PV+ neurons were observed, mostly involving secondary and more distal dendrites (0.5-1.0 microm thick). Dendritic gap junctions were often in close proximity to PV+ chemical synapses. Six gap junctions were observed between PV+ axon terminals. In most cases, one or both of these terminals formed synapses with the perikarya of principal neurons. This is the first study to describe dendritic gap junctions interconnecting PV+ interneurons in the basolateral amygdala. It also provides the first documentation of gap junctions between interneuronal axon terminals in the mammalian forebrain. These data provide the anatomical basis for a PV+ network that may play a role in the generation of rhythmic oscillations in the BLa during emotional arousal.

Amygdala↗
PubMed2005

Cooperative activation of D1 and D2 dopamine receptors enhances a hyperpolarization-activated inward current in layer I interneurons.

Layer I of the neocortex comprises axonal processes from widespread regions of the brain and a unique population of GABAergic interneurons. Dopamine is known to directly depolarize layer I interneurons, but the underlying mechanism is unclear. Using whole-cell recording techniques in neocortical brain slices, we have examined how dopamine increases excitability of layer I interneurons in postnatal day 7-11 rats. Dopamine (30 microm) caused a 10 mV depolarization of layer I neurons. Paradoxically, neither the D1-like receptor agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide (SKF81297) (1-10 microm) nor the D2-like agonist quinpirole (10 microm) produced a significant depolarization. Depolarization was observed when SKF81297 and quinpirole were coapplied. When G-protein betagamma subunits were included in the recording pipette, D1 but not D2 agonists depolarized layer I neurons. Bath application of 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, a specific blocker of inwardly rectifying hyperpolarization-activated current (Ih) channels, hyperpolarized the neurons and occluded the action of dopamine. Voltage-clamp analysis demonstrated that dopamine increased the amplitude and shifted the voltage dependence of activation of Ih. These results indicate that Ih contributes to the resting potential of layer I interneurons and is subject to modulation by dopamine.

Action Potentials↗
PubMed2004

Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro.

Gamma frequency (30-100 Hz) network oscillations occur in the intact hippocampus during awake, attentive behavior. Here, we explored the underlying cellular mechanisms in an in vitro model of persistent gamma-frequency oscillations, induced by bath application of 20 microm carbachol in submerged hippocampal slices at 30 +/- 1 degrees C. Current-source density analysis of the field oscillation revealed a prominent alternating sink-source pair in the perisomatic and apical dendritic regions of CA3. To elucidate the active events generating these extracellular dipoles, we examined the firing properties of distinct neuron types. Visually guided unit recordings were obtained from individual CA3 neurons followed by intracellular labeling for anatomical identification. Pyramidal cells fired at 2.82 +/- 0.7 Hz, close to the negative peak of the oscillation (0.03 +/- 0.65 msec), and often in conjunction with a negative spike-like component of the field potential. In contrast, all phase-coupled interneurons fired after this negative peak. Perisomatic inhibitory interneurons fired at high frequency (18.1 +/- 2.7 Hz), shortly after the negative peak (1.97 +/- 0.95 msec) and were strongly phase-coupled. Dendritic inhibitory interneurons fired at lower frequency (8.4 +/- 2.4 Hz) and with less fidelity and a longer delay after the negative peak (4.3 +/- 1.1 msec), whereas interneurons with cell body in the stratum radiatum often showed no phase relationship with the field oscillation. The phase and spike time data of individual neurons, together with the current-source density analysis, support a synaptic feedback model of gamma oscillations primarily involving pyramidal cells and inhibitory cells targeting their perisomatic region.

Action Potentials↗
PubMed2004

D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons.

Striatal cholinergic interneurons are critical elements of the striatal circuitry controlling motor planning, movement, and associative learning. Intrastriatal release of dopamine and inhibition of interneuron activity is thought to be a critical link between behaviorally relevant events, such as reward, and alterations in striatal function. However, the mechanisms mediating this modulation are unclear. Using a combination of electrophysiological, molecular, and computational approaches, the studies reported here show that D2 dopamine receptor modulation of Na+ currents underlying autonomous spiking contributes to a slowing of discharge rate, such as that seen in vivo. Four lines of evidence support this conclusion. First, D2 receptor stimulation in tissue slices reduced the autonomous spiking in the presence of synaptic blockers. Second, in acutely isolated neurons, D2 receptor activation led to a reduction in Na+ currents underlying pacemaking. The modulation was mediated by a protein kinase C-dependent enhancement of channel entry into a slow-inactivated state at depolarized potentials. Third, the sodium channel blocker TTX mimicked the effects of D2 receptor agonists on pacemaking. Fourth, simulation of cholinergic interneuron pacemaking revealed that a modest increase in the entry of Na+ channels into the slow-inactivated state was sufficient to account for the slowing of pacemaker discharge. These studies establish a cellular mechanism linking dopamine and the reduction in striatal cholinergic interneuron activity seen in the initial stages of associative learning.

Acetylcholine↗
PubMed2004

A mosaic of functional kainate receptors in hippocampal interneurons.

Although some physiological functions of kainate receptors (KARs) still remain unclear, recent advances have highlighted a role in synaptic physiology. In hippocampal slices, kainate depresses GABA-mediated synaptic inhibition and increases the firing rate of interneurons. However, the sensitivity to agonists of these responses differs, suggesting that the presynaptic and somatic KARs have a distinct molecular composition. Hippocampal interneurons express several distinct KAR subunits that can assemble into heteromeric receptors with a variety of pharmacological properties and that, in principle, could fulfill different roles. To address which receptor types mediate each of the effects of kainate in interneurons, we used new compounds and mice deficient for specific KAR subunits. In a recombinant assay, 5-carboxyl-2,4-di-benzamido-benzoic acid (NS3763) acted exclusively on homomeric glutamate receptor subunit 5 (GluR5), whereas 3S,4aR,6S,8aR-6-((4-carboxyphenyl)methyl) 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884) antagonized homomeric GluR5 and any heteromeric combination containing GluR5 subunits. In hippocampal slices, LY382884, but not NS3763, was able to prevent kainate-induced depression of evoked IPSC. In contrast, neither prevented the concomitant increase in spontaneous IPSC frequency. The selectivity of these compounds was seen additionally in knock-out mice, such that they were inactive in GluR5-/- mice but completely effective in GluR6-/- mice. Our data indicate that in wild-type mice, CA1 interneurons express heteromeric GluR6 -KA2 receptors in their somatic compartments and GluR5-GluR6 or GluR5-KA2 at presynaptic terminals. However, functional compensation appears to take place in the null mutants, a new pharmacological profile emerging more compatible with the activity of homomeric receptors in both compartments: GluR5 in GluR6-/- mice and GluR6 in GluR5-/- mice.

Animals↗
PubMed2005

Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus.

Among the electrophysiological properties differentiating stratum oriens horizontal interneurons from pyramidal neurons of the CA1 hippocampal subfield are the more depolarized resting potential and the higher input resistance; additionally, these interneurons are also less sensitive to ischemic damage than pyramidal cells. A differential expression of pH-sensitive leakage potassium channels (TASK) could contribute to all of these differences. To test this hypothesis, we studied the expression and properties of TASK channels in the two cell types. Electrophysiological recordings from acute slices showed that barium- and bupivacaine-sensitive TASK currents were detectable in pyramidal cells but not in interneurons and that extracellular acidification caused a much stronger depolarization in pyramidal cells than in interneurons. This pyramidal cell depolarization was paralleled by an increase of the input resistance, suggesting the blockade of a background conductance. Single-cell reverse transcription-PCR experiments showed that the expression profile of TASK channels differ between the two cell types and suggested that these channels mediate an important share of the leakage current of pyramidal cells. We suggest that the different expression of TASK channels in these cell types contribute to their electrophysiological differences and may result in cell-specific sensitivity to extracellular acidification in conditions such as epilepsy and ischemia.

Anesthetics, Local↗
PubMed2006

A 3-synapse positive feedback loop regulates the excitability of an interneuron critical for sensitization in the leech.

Sensitization of reflexive shortening in the leech has been linked to serotonin (5-HT)-induced changes in the excitability of a single interneuron, the S cell. This neuron is necessary for sensitization and complete dishabituation of reflexive shortening, during which it contributes to the sensory-motor reflex. The S cell does not contain 5-HT, which is released primarily from the Retzius (R) cells, whose firing enhances S-cell excitability. Here, we show that the S cell excites the R cells, mainly via a fast disynaptic pathway in which the first synapse is the electrical junction between the S cell and the coupling interneurons, and the second synapse is a glutamatergic synapse of the coupling interneurons onto the R cells. The S cell-triggered excitatory postsynaptic potential in the R cell diminishes and nearly disappears in elevated concentrations of divalent cations because the coupling interneurons become inexcitable under these conditions. Serotonin released from the R cells feeds back on the S cell and increases its excitability by activating a 5-HT7-like receptor; 5-methoxytryptamine (5-MeOT; 10 microM) mimics the effects of 5-HT on S cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide (10 microM) and SB-269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol] (5 microM). This feedback loop may be critical for the full expression of sensitization of reflexive shortening.

Animals↗
PubMed2006

Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels.

Noxious stimuli are sensed and carried to the spinal cord dorsal horn by A delta and C primary afferent fibers. Some of this input is relayed directly to supraspinal sites by projection neurons, whereas much of the input impinges on a heterogeneous population of interneurons in lamina II. Previously, we demonstrated that G-protein-gated inwardly rectifying potassium (GIRK) channels are expressed in lamina II of the mouse spinal cord and that pharmacologic ablation of spinal GIRK channels selectively blunts the analgesic effect of high but not lower doses of intrathecal mu-opioid receptor (MOR) agonists. Here, we report that GIRK channels formed by GIRK1 and GIRK2 subunits are found in two large populations of lamina II excitatory interneurons. One population displays relatively large apparent whole-cell capacitances and prominent GIRK-dependent current responses to the MOR agonist [D-Ala2,N-MePhe4,Gly-ol5] -enkephalin (DAMGO). A second population shows smaller apparent capacitance values and a GIRK-dependent response to the GABA(B) receptor agonist baclofen, but not DAMGO. Ultrastructural analysis revealed that GIRK subunits preferentially label type I synaptic glomeruli, suggesting that GIRK-containing lamina II interneurons receive prominent input from C fibers, while receiving little input from A delta fibers. Thus, excitatory interneurons in lamina II of the mouse spinal cord can be subdivided into different populations based on the neurotransmitter system coupled to GIRK channels. This important distinction will afford a unique opportunity to characterize spinal nociceptive circuitry with defined physiological significance.

Analgesics, Opioid↗
PubMed2005

Locus ceruleus activation suppresses feedforward interneurons and reduces beta-gamma electroencephalogram frequencies while it enhances theta frequencies in rat dentate gyrus.

The locus ceruleus is activated by novel stimuli, and its activation promotes learning and memory. Phasic activation of locus ceruleus neurons by glutamate enhances the dentate gyrus population spike amplitude and results in long-term potentiation of synaptic responses recorded after 24 h. Cholinergic activation of locus ceruleus neurons increases hippocampal . At the level of the cellular network, it is not clear how the potentiating effects of norepinephrine are mediated. Previous studies show that exogenous norepinephrine enhances inhibitory interneuron firing in the dentate gyrus. This finding appears at odds with evidence for potentiation. In this study, natural release of norepinephrine was induced by glutamate activation of locus ceruleus while we recorded EEGs and physiologically identified interneurons in the dentate gyrus of urethane-anesthetized rats. Feedforward neurons were inhibited (approximately 1-2 min) by locus ceruleus activation. Feedback interneurons showed both increased and decreased activity, whereas granule cells increased firing as predicted by evoked potential studies. EEG results replicated an increase in power (4-8 Hz) with locus ceruleus activation, but the effect with glutamatergic locus ceruleus activation was transient (approximately 1-2 min). Beta-gamma Frequencies were also transiently suppressed. Together, the data suggest that locus ceruleus activation enhances the throughput of concomitant sensory input by reducing feedforward inhibitory interneuron activity, which may reduce "binding" in existing cell assemblies, and enhances the conditions for synaptic plasticity through disinhibition, promotion of 4-8 Hz , and noradrenergic potentiation to facilitate the building of new representations.

Animals↗
PubMed2006

Cortical inputs and GABA interneurons imbalance projection neurons in the striatum of parkinsonian rats.

The striatum receives massive cortical excitatory inputs and is densely innervated by dopamine. Striatal projection neurons form either the direct or indirect pathways. Models of Parkinson's disease propose that dopaminergic degeneration imbalances both pathways, although direct electrophysiological evidence is lacking. Here, striatal neurons were identified by electrophysiological criteria and Neurobiotin labeling combined with either immunohistochemistry or in situ hybridization. Their spontaneous discharge activity and spike response to cortical stimulation were recorded in vivo in anesthetized rats rendered hemi-parkinsonian by 6-hydroxydopamine. We showed that striatonigral neurons (direct pathway) were inhibited whereas striatopallidal neurons (indirect pathway) were activated by dopaminergic lesion. We also identified, with antidromic stimulations, corticostriatal neurons that preferentially innervate striatonigral or striatopallidal neurons and showed that dopaminergic depletion selectively decreased the spontaneous activity of the former. Therefore, dopamine degeneration induces a cascade of imbalances that spread out of the basal ganglia and affect the whole basal ganglia-thalamo-cortical circuits. Fast-spiking GABA interneurons provide potent feedforward inhibition of striatal projection neurons. We showed here that these interneurons narrowed the time window of the responses of projection neurons to cortical stimulation. In the dopamine-depleted striatum, because the intrinsic activity of these interneurons was not altered, their feedforward inhibition worsened the striatal imbalance. Indeed, the time window of the evoked responses was narrower for striatonigral neurons and wider for striatopallidal neurons. Therefore, after dopaminergic depletion, cortical inputs and GABA interneurons might imbalance striatal projection neurons and represent two novel nondopaminergic mechanisms that might secondarily contribute to the pathophysiology of Parkinson's disease.

Animals↗
PubMed2006

Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny stellate cells is mediated by a small number of fast-spiking interneurons.

Inhibitory and excitatory neurons located in rodent barrel cortex are known to form functional circuits mediating vibrissal sensation. Excitatory neurons located in a single barrel greatly outnumber interneurons, and form extensive reciprocal excitatory synaptic contacts. Inhibitory and excitatory networks must interact to shape information ascending to cortex. The details of these interactions, however, have not been completely explored. Using paired intracellular recordings, we studied the properties of synaptic connections between spiny neurons (i.e., spiny stellate and pyramidal cells) and interneurons, as well as integration of thalamocortical (TC) input, in layer IV barrels of rat thalamocortical slices. Results show the following: (1) the strength of unitary excitatory connections of spiny neurons is similar among different targets; (2) although inhibition from regular-spiking nonpyramidal interneurons to spiny neurons is comparable in strength to excitatory connections, inhibition mediated by fast-spiking (FS) interneurons is 10 times more powerful; (3) TC EPSPs elicit reliable and precisely timed action potentials in FS neurons; and (4) a small number of FS neurons mediate thalamocortical feedforward inhibition in each spiny neuron and can powerfully shunt TC-mediated excitation. The ready activation of FS cells by TC inputs, coupled with powerful feedforward inhibition from these neurons, would profoundly influence sensory processing and constrain runaway excitation in vivo.

Action Potentials↗
PubMed2006

Characterization of AMPA receptors targeted by the climbing fiber transmitter mediating presynaptic inhibition of GABAergic transmission at cerebellar interneuron-Purkinje cell synapses.

The climbing fiber (CF) neurotransmitter not only excites the postsynaptic Purkinje cell (PC) but also suppresses GABA release from inhibitory interneurons converging onto the same PC depending on AMPA-type glutamate receptor (AMPAR) activation. Although the CF-/AMPAR-mediated inhibition of GABA release provides a likely mechanism boosting the CF input-derived excitation, how the CF transmitter reaches target AMPARs to elicit this action remains unknown. Here, we report that the CF transmitter diffused from its release sites directly targets GluR2/GluR3 AMPARs on interneuron terminals to inhibit GABA release. A weak GluR3-AMPAR agonist, bromohomoibotenic acid, produced excitatory currents in the postsynaptic PCs without presynaptic inhibitory effect on GABAergic transmission. Conversely, a specific inhibitor of the GluR2-lacking/Ca2+-permeable AMPARs, philanthotoxin-433, did not affect the CF-induced inhibition but suppressed AMPAR-mediated currents in Bergmann glia. A low-affinity GluR antagonist, gamma-D-glutamylglycine, or retardation of neurotransmitter diffusion by dextran reduced the inhibitory action of CF-stimulation, whereas blockade of glutamate transporters enhanced the CF-induced inhibition. The results suggest that the CF transmitter released after repeated stimulation overwhelms local glutamate uptake and thereby diffuses from the release site to reach GluR2/GluR3 AMPARs on nearby interneuron terminals. Double immunostaining showed that GluR2/3 subunits and glutamate decarboxylase or synaptophysin are colocalized at the perisomatic GABAergic processes surrounding PCs. Finally, electron microscopy detected specific immunoreactivity for GluR2/3 at the presynaptic terminals of symmetric axosomatic synapses on the PC. These findings demonstrate that the CF transmitter directly inhibits GABA release from interneurons to the PC, relying on extrasynaptic diffusion and local heterogeneity in AMPAR subunit compositions.

Animals↗
PubMed1996

Evidence of synaptic contacts of nociceptive primary afferent central terminals on GABAergic interneurons in the substantia gelatinosa.

Recently, we showed that capsaicin induced the degeneration of not only glomerular CI terminals but also of non-glomerular CI terminals making presynaptic contact with interneuronal soma. Studies of the nature of interneurons making contact by nonglomerular CI terminals should provide important information to facilitate our understanding of the processing of nociceptive impulses in the substantia gelatinosa. The most likely candidate molecule involved in this process in these interneurons is gamma-aminobutylic acid (GABA). Therefore, ultrastructural relationships between nonglomerular CI terminals land GABAergic interneuronal soma in the mouse substatia gelatinosa were examined by an immunocytochemical method using an antibody to GABA. Terminals with the same profiles as the CI terminals, i.e., slender, sinuous and scalloped terminals filled with clear synaptic vesicles, were found to make synaptic contacts with GABA-immunoreactive somata. Thus, nociceptive primary afferents are suggested to modulate pain transmission by themselves via GABAergic neurons in the substantia gelatinosa.

Animals↗
PubMed2000

Temporal changes in the excitability of the reciprocal inhibitory interneurones preceding cocontraction of the antagonistic muscle in the human wrist.

The supraspinal control of reciprocal inhibitory interneurones preceding cocontraction of antagonistic muscles in the human wrist was investigated in 5 subjects. The method combined a reaction time task paradigm and a technique for conditioning the H-reflex. Unconditioned H-reflexes were elicited from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles by using electrical stimulation to median and radial nerves. The conditioned H-reflex of the FCR muscle was obtained by simultaneous electrical stimulation to the median and the radial nerves. While subjects performed the bilateral isometric cocontraction task, excitabilities of the alpha motoneurone pools and that of the reciprocal inhibitory interneurones were assessed by the unconditioned and conditioned H-reflex, respectively. Alpha mononeuron pools of FCR and ECR muscles were facilitated starting from approximately 50 msec. preceeding EMG activities. Reciprocal inhibitory interneurones which suppressed FCR alpha motoneurones were disinhibited at almost same time. The present results suggested that supraspinal control of the reciprocal inhibitory interneurones preceding antagonist cocontraction is different from that of preceding agonist contraction.

Adult↗
PubMed1999

Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons.

Exploring the organization and function of local inhibitory networks is an essential step on the way to understand the principles of brain operation. We show here that molecular layer inhibitory interneurons of the guinea pig cerebellar cortex are organized as local networks, generating synchronous activity. Simultaneous recording from two adjacent interneurons revealed a direct current flow between synchronized pairs of neurons. Blocking inhibitory or excitatory synaptic transmission did not alter the synchronization. The electrotonic coupling coefficient (average 0.1) depended mainly on the input resistance of the postsynaptic cell, indicating a homogenous coupling resistance between different pairs. A presynaptic action potential generated a short, attenuated spikelet in the postsynaptic cell. The passive current flow was amplified by voltage-dependent intrinsic currents to create a reciprocal interplay between the presynaptic and postsynaptic cells. This interplay results in a time window for synchronization that is wider than expected from the duration of the spikelet. Intracellular staining with biocytin revealed high incidence of dye coupling. Furthermore, the interneurons located superficially in the molecular layer tend to form larger networks compared with the inner interneurons. We propose that weakly coupled inhibitory networks can generate loosely synchronous activity, which results from the interaction of electrical coupling and intrinsic currents.

Animals↗
PubMed1999

Two types of interneurons in the cat visual thalamus are distinguished by morphology, synaptic connections, and nitric oxide synthase content.

The distribution of the neuronal form of the nitric oxide-synthesizing enzyme, brain nitric oxide synthase (BNOS), was examined in the cat thalamus by using immunocytochemical techniques. BNOS was found in both cells and fibers throughout the visual thalamus. BNOS-stained cells were found consistently in the C laminae of the lateral geniculate nucleus (LGN), the pulvinar nucleus, and the lateral posterior nucleus (LP). In the A laminae of the LGN, variable numbers of BNOS-stained cells also could be detected. BNOS-stained cells were identified as a subset of interneurons because they all stained for glutamic acid decarboxylase (GAD), but not all GAD-stained cells contained BNOS. The average soma area of BNOS-stained cells was slightly greater than the average soma area of GAD-stained cells. BNOS-stained cells display a distinctive dendritic morphology, which is consistent with previous descriptions of class V neurons (Updyke [1979] J. Comp. Neurol. 186:603-619); they have widespread but fairly sparse arbors of thin, somewhat beaded dendrites. BNOS-stained cells participate in a distinct synaptic circuitry. Although many GAD-stained profiles are filled with vesicles and participate in complex synaptic arrangements, known as glomeruli, BNOS-stained dendrites contain small clusters of vesicles and form dendrodendritic contacts in the extraglomerular neuropil. Thus, there appear to be at least two types of gamma-aminobutyric acidergic interneurons in the visual thalamus of the cat. Interneurons that do not contain BNOS (class III morphology) may exert their effects primarily within synaptic glomeruli (Hamos et al. [1985] Nature 317:618-621), whereas interneurons that contain BNOS (class V morphology) contribute primarily to the extraglomerular neuropil.

Animals↗
PubMed2000

Dependence of GABAergic synaptic areas on the interneuron type and target size.

In the neostriatum, several types of interneuron with distinct firing patterns and expression of neuroactive substances are known to exist. We found two types of neostriatal interneurons, parvalbumin-containing fast-spiking (FS) cells and somatostatin-containing low-threshold spike (LTS) cells to both be immunoreactive for GABA at their axon terminals in immersion-fixed brain slices from rat. To reveal the differences in synaptic connections between these two types of GABAergic interneurons, the postsynaptic target and their synaptic structure were compared by three-dimensional reconstructions from electron microscopic images of intracellularly stained axon terminals. FS cells made a greater proportion of synaptic contacts onto somata than LTS cells. Although terminal boutons of FS and LTS cells were similar in volume, their synaptic junctional areas differed in size distribution and relation to the dimensions of postsynaptic dendritic shafts or spines. Whereas the synaptic junctional areas of FS cells (0.024-0.435 microm(2); n = 28) sharply and linearly increased with the circumference of the postsynaptic dendrites or spines (0.939-5.146 microm), the slope for the junctional area of LTS cells (0.02-0.103 microm(2); n = 29) against circumference (0.844-4.252 microm) was less steep, and a much weaker correlation was seen. In addition to the differences in firing patterns, expressed molecules, axonal arborizations, and postsynaptic targets, this variation in dependency of the synaptic area on the target size suggests functional differentiation of GABAergic interneurons.

Action Potentials↗
PubMed2000

Intracellular Ca2+ dynamics during spontaneous and evoked activity of leech heart interneurons: low-threshold Ca currents and graded synaptic transmission.

In oscillatory neuronal networks that pace rhythmic behavior, Ca(2+) entry through voltage-gated Ca channels often supports bursting activity and mediates graded transmitter release. We monitored simultaneously membrane potential and/or ionic currents and changes of Ca fluorescence (using the fluorescence indicator Ca Orange) in spontaneously active and experimentally manipulated oscillator heart interneurons in the leech. We show that changes in Ca fluorescence in these interneurons during spontaneous bursting and evoked activity reflect the slow wave of that activity and that these changes in Ca fluorescence are mediated by Ca(2+) entry primarily through low-threshold Ca channels. Spatial and temporal maps of changes in Ca fluorescence indicate that these channels are widely distributed over the neuritic tree of these neurons. We establish a correlation between the amount of transmitter released, as estimated by the integral of the postsynaptic current, and the change in Ca fluorescence. In experiments in which we were able to record presynaptic low-threshold Ca currents, associated IPSCs, and presynaptic changes in Ca fluorescence from fine neuritic branches of heart interneurons near their region of synaptic contact with their contralateral partner, there was a close association between the rise in Ca fluorescence and the rise of the postsynaptic conductance. The changes in Ca fluorescence that we record at the end of fine neuritic branches appear to reflect changes in [Ca(2+)](i) that mediate graded synaptic release in leech heart interneurons. These results indicate that widely distributed low-threshold Ca currents play an important role in generating rhythmic activity and in mediating graded transmitter release.

Animals↗