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PubMed2001

Substance P receptor expression by inhibitory interneurons of the rat hippocampus: enhanced detection using improved immunocytochemical methods for the preservation and colocalization of GABA and other neuronal markers.

Two unresolved issues regarding the identification and characterization of hippocampal interneurons were addressed in this study. One issue was the longstanding inability to detect gamma-aminobutyric acid (GABA) in the somata of several hippocampal interneuron subpopulations, which has prevented the unequivocal identification of all hippocampal interneurons as GABA neurons. The second issue was related to the identification of the hippocampal interneurons that constitutively express substance P (neurokinin-1) receptors (SPRs). The recent development of neurotoxins that specifically target SPR-expressing cells suggests that it may be possible to destroy hippocampal inhibitory interneurons selectively for experimental purposes. Although SPRs are apparently expressed in the hippocampus only by interneurons, colocalization studies have found that most interneurons of several subtypes and hippocampal subregions appear SPR-negative. Thus, the identities and locations of the inhibitory interneurons that are potential targets of an SPR-directed neurotoxin remain in doubt. Using newly developed methods designed to copreserve and colocalize GABA and polypeptide immunoreactivities with increased sensitivity, the authors report that virtually all hippocampal interneuron somata that are immunoreactive for parvalbumin (PV), calbindin, calretinin, somatostatin (SS), neuropeptide Y, cholecystokinin, and vasoactive intestinal peptide exhibited clearly detectable, somal, GABA-like immunoreactivity (LI). Hippocampal SPR-LI was detected only on the somata and dendrites of GABA-immunopositive interneurons. All glutamate receptor subunit 2-immunoreactive principal cells, including dentate granule cells, hilar mossy cells, and hippocampal pyramidal cells, were devoid of detectable SPR-LI, even after prolonged electrical stimulation of the perforant pathway that induced the expression of other neuronal proteins in principal cells. Thus, hippocampal interneurons of all subtypes and subregions were found to be SPR-immunoreactive, including the PV-positive interneurons of the dentate hilus and hippocampus, and the SS-positive cells of area CA1, both of which were previously reported to lack SPR-LI. Only minor proportions of hippocampal interneurons appeared clearly devoid of detectable SPR-LI. These results demonstrate for the first time that all identified interneuron subpopulations of the rat hippocampus are GABA-immunoreactive, and that many inhibitory interneurons of all subtypes in all subregions of the rat hippocampus express SPRs constitutively.

Animals↗
PubMed1997

Effect of transient cerebral ischemia on gamma-aminobutyric acidA receptor alpha 1-subunit-immunoreactive interneurons in the gerbil CA1 hippocampus.

Following transient cerebral ischemia, pyramidal cells within area CA1 of the hippocampus exhibit delayed neuronal death. While interneurons within this sector continue to survive long-term, there is evidence that some interneurons in area CA1 are vulnerable to damage. To determine the nature of vulnerability in a neurochemically heterogeneous population of interneurons throughout area CA1, we examined the labeling of gamma-aminobutyric acid (GABA)ergic interneurons with an antibody to the GABAA receptor alpha 1-subunit 1-35 days following cerebral ischemia in the Mongolian gerbil. Unlike some other GABA interneuron markers, this antibody labels both the dendrites and soma of interneurons, allowing dendritic structure to be examined. Three to four days following ischemia, the pyramidal cells in area CA1 had degenerated, and the alpha 1-subunit-positive interneurons in all layers of area CA1 had developed severely beaded dendrites. At longer survival times (21-35 days), the alpha 1-subunit-immunolabeled dendrites of these interneurons had a fragmented appearance. In contrast, interneurons bordering str. oriens and alveus typically exhibited normal dendritic morphology. Despite the pathologic changes, there was no evidence of interneuron loss in area CA1 up to 35 days post-ischemia. Normal interneuron morphology was also observed in area CA3 and dentate gyrus, regions where neither pyramidal neurons nor granule cells, respectively, die following 5 min of cerebral ischemia. To determine if the ischemia-induced changes in interneuron morphology could be prevented, diazepam was administered 30 and 90 min following ischemia. Diazepam produces long-term neuroprotection of area CA1 pyramidal neurons. In gerbils sacrificed 35 days after ischemia, diazepam markedly attenuated the dendritic beading of the area CA1 interneurons. In addition, the dendrites did not display the fragmented labeling by the alpha 1-subunit antibody. Thus, despite their long-term survival, CA1 hippocampal interneurons in the gerbil can express severe structural abnormalities after transient cerebral ischemia coincident with pyramidal cell degeneration, and the injury to the dendrites can be prevented by the neuroprotectant diazepam.

Animals↗
PubMed2004

Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord.

Electrophysiological and morphological properties of genetically identified spinal interneurons were examined to elucidate their possible contribution to locomotor-like rhythmic activity in 1- to 4-day-old mice. In the transgenic mice used in our study, the HB9 promotor controlled the expression of the reporter gene enhanced green fluorescent protein (eGFP), giving rise to GFP+ motoneurons and ventral interneurons. However, only motoneurons and a small group of bipolar, GFP+ interneurons expressed the HB9 protein. The HB9(+)/GFP+ interneurons were clustered close to the medial surface in lamina VIII along segments L1-L3. The correlation between activity pattern in these visually identified interneurons and motoneuron output was examined using simultaneous whole cell and ventral root recordings. Neurochemically induced rhythmic membrane depolarizations in HB9/GFP interneurons were synchronous with ventral root rhythms, indicating that the interneurons received synaptic inputs from rhythm-generating networks. The frequency of excitatory postsynaptic currents significantly increased during ventral root bursts, but there was no change in the frequency of inhibitory postsynaptic currents during the cycle period. These data implied that HB9/GFP interneurons received primarily excitatory inputs from rhythmogenic interneurons. Neurobiotin-filled axon terminals were in close apposition to other neurons in the cluster and to motoneuron dendrites, raising the possibility that HB9/GFP interneurons formed synaptic connections with each other and with motoneurons. The expression of the vesicular glutamate transporter 2 in axon terminals of HB9/GFP interneurons indicated that these were glutamatergic interneurons. Our findings suggest that the visually identified HB9/GFP interneurons are premotor excitatory interneurons and putative constituents of networks generating locomotor rhythms in the mammalian spinal cord.

Animals↗
PubMed1977

Interconnections of identified multiaction interneurons in buccal ganglia of Aplysia.

1. The 26 identified neurons of Aplysia buccal ganglia include 4 interneurons and their follower cells. Each interneuron makes cholinergic synaptic connections on eight identified ipsilateral follower neurons. Each interneuronal action potential also produces a zero-latency, Mg-intensitive electrotonic coupling potential in one cholinergic and electrotonic input from the interneurons. Electrotonic connections are bidirectional and nonrectifying. 2. Ipsilateral pairs of interneurons receive extensive common synaptic input from several unidentified neurons: each interneuron also receives some input not received by the other. These pairs are linked by bidirectional nonrectifying electronic coupling which is insensitive to high Mg. As a consequence of this organization, ipsilateral interneuron pairs can fire a) independently, or b) synchronously, or c) one active interneuron can depolarize the other. 3. Each follower receiving synaptic input from one ipsilateral interneuron also receives similar input from the other interneuron. Common follower cells thus receive a) asynchronous PSPs, or b) large summated PSPs, or c) an increased number of PSPs from each interneuron. The latter two modes constitute feed-forward summation of interneuronal action. 4. Interneuronal output is confined to ipsilateral neurons. Symmetric pairs of interneurons are coordinated by common inputs and are not directly interconnected by either chemical or electrotonic synapses. Synchrony of firing of symmetric pairs is, therefore, looser than that of ipsilateral pairs.

Action Potentials↗
PubMed1985

Nonspiking local interneuron in the motor pattern generator for the crayfish swimmeret.

We describe a type of nonspiking premotor local interneuron (interneuron IA) in the abdominal nervous system of Pacifasticus leniusculus. All of its branches are restricted to one side of the midline. These interneurons are identifiable and occur as bilateral pairs, one neuron on each side of abdominal ganglia 3, 4, and 5. The membrane potential of interneuron IA oscillated in phase with the swimmeret rhythm, a motor pattern generated in each of these ganglia, because the neuron received postsynaptic potentials in phase with the rhythm. Sustained hyperpolarization of an individual interneuron IA initiated generation of the swimmeret rhythm in all the ganglia of a quiescent nervous system. Sustained depolarization stopped the swimmeret rhythm in all the active ganglia of a nervous system that was generating the rhythm. Currents injected into one interneuron reset the rhythm. Comparisons of the shapes of the IA interneurons in different ganglia showed that they are similar to each other and distinct from other local interneurons in these ganglia. Interneuron IA has a large integrative segment and relatively few branches that are largely restricted to the lateral neuropil, to which all other kinds of swimmeret neurons also project. We conclude that this interneuron occurs only once in each hemiganglion in abdominal segments 3, 4, and 5, and that it is identifiable. Furthermore, this interneuron is an essential component of the circuit in each hemiganglion that generates the swimmeret rhythm. The interneuron was dye coupled to a particular identifiable motor neuron and not to any other neurons. The motor neuron was not dye-coupled to any other local interneurons. The ability of this motor neuron to reset the rhythm is attributed to its being electrically coupled to interneuron IA in its ganglion.

Animals↗
PubMed1987

Synaptic potentials of primary afferent fibers and motoneurons evoked by single intermediate nucleus interneurons in the cat spinal cord.

Spike-triggered averaging of dorsal and ventral root potentials was used in anesthetized cats to disclose possible synaptic connections of spinal interneurons in the intermediate nucleus with afferent fibers and/or motoneurons. With this method we have been able to document the existence of a distinct group of interneurons whose activity was associated with the recording of inhibitory potentials in the ventral roots (iVRPs), but not with negative dorsal root potentials (nDRPs). The iVRPs had mean durations of 60.8 +/- 22.1 ms and latencies between 1.7 and 5.1 ms relative to the onset of the interneuronal spikes. Within this group of neurons it was possible to characterize two categories depending on their responses to segmental inputs. Most type A interneurons were mono- or disynaptically activated by group I muscle afferents and polysynaptically by low threshold (1.08-1.69 X T) cutaneous fibers. Type B interneurons were instead polysynaptically activated by group II muscle and by cutaneous fibers with thresholds ranging from 1.02 to 3.1 X T. Whenever tested, both type A and B interneurons could be antidromically activated from Clarke's columns. There was a second group of interneurons whose activity was associated with the generation of both iVRPs and nDRPs. These potentials had mean durations of 107.5 +/- 35.6 and 131.5 +/- 32 ms, respectively, and onset latencies between 1.7 and 6.1 ms. The interneurons belonging to this group, which appear not to send axonal projections to Clarke's column, could be classified in three categories depending on their responses to peripheral inputs. Type C interneurons responded mono- or disynaptically to group I muscle volleys and polysynaptically to intermediate threshold (1.22-2.7 X T) cutaneous afferents. Type D interneurons were polysynaptically activated by group II muscle afferents (2.3-8.5 X T) and by intermediate threshold (1.4-3 X T) cutaneous fibers and type E interneurons only by group I muscle afferents with mono- or disynaptic latencies. A third group of interneurons produced nDRPs without iVRPs. The nDRPs had onset latencies varying from 1.9 to 6.2 ms and mean durations of 130.0 +/- 34.6 ms. These neurons (type F) showed spontaneous and evoked bursts of activity and were not antidromically activated from Clarke's column. They responded to stimulation of low- and intermediate-threshold cutaneous fibers (1.04-2.9 X T) with mono- and polysynaptic latencies, but not by group I muscle fibers. Type F interneurons appear to be located in more superficial layers than all the other interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Functional properties of spinal interneurons activated by muscular free nerve endings and their potential contributions to the clasp-knife reflex.

1. The goal of this study was to characterize the functional properties of spinal interneurons that are excited by muscular free nerve endings and to assess their contributions to the clasp-knife reflex. 2. The patterns of activity of 82 spinal interneurons that were excited by squeezing the Achilles tendon or manipulation of the muscle surfaces, preferential stimuli for muscular free nerve endings, were extracellularly recorded in lamina V-VII of the L5-S1 spinal cord in decerebrated and spinalized cats. 3. Interneurons were uniformly excited by increases in muscular length and force. Responses to muscle stretch exhibited gradual decay during maintained stretch, afterdischarge after stretch release, and adaptation to repeated stretch. Responses to isometric contraction induced by electrical stimulation of motor axons was also prolonged after contraction, but did not decay during maintained contraction. For similar increases in force, stretch evoked greater excitation than contraction, indicating that both stretch and contraction contributed to interneuronal activity. Overall, the time course and magnitude of the interneuronal responses to stretch and contraction paralleled the time course and magnitude of the clasp-knife reflex. 4. Interneurons were powerfully excited by muscular free nerve endings, which mediate the clasp-knife reflex, and by cutaneous receptors. Only occasionally were they excited by primary spindle or Golgi tendon organ afferents, which suggests that activation of muscular free nerve endings mediated the interneuronal responses to stretch and contraction. 5. Simultaneous recordings of interneuronal activity and the clasp-knife reflex revealed a broad correlation between interneuronal activity and clasp-knife inhibition. 6. Because the patterns of activity of free nerve ending-responsive interneurons during stretch and contraction were similar to the clasp-knife reflex, were closely correlated with clasp-knife inhibition during simultaneous interneuronal and reflex recordings, and were powerfully excited by muscular free nerve endings, it is likely that the interneurons described above contributed to the clasp-knife reflex. 7. In contrast, a small number (n = 16) of interneurons were recorded that were only weakly excited by muscular free nerve endings but strongly excited by group I afferents, exhibited less spontaneous and evoked activity, and had significantly different responses to stretch and contraction. These interneurons are less likely to have contributed to the clasp-knife reflex.

Animals↗
PubMed1993

Interneurons in rat hippocampus after cerebral ischemia. Morphometric, functional, and therapeutic investigations.

This review describes the neuropathology and pathophysiology of interneurons in dorsal hippocampus of the adult rat subjected to transient global cerebral ischemia. The object is to verify if the interneurons die or survive after an ischemic insult, and study if ischemia changes GABA inhibition in the period preceding delayed CA1 pyramidal cell death. The findings are discussed from the point of the hypothesis that loss of GABA inhibition may result in excitatory hyperactivity (possibly epilepsy) and excitotoxic glutamate release. Thereby, early ischemic damage to interneurons may exacerbate the ischemic process resulting in the major and delayed CA1 cell death in hippocampus. Interneurons, located in dentate hilus, and a small number of interneurons located in the mossy fiber layer are selectively lost after ischemia. These interneurons contain somatostatin and neuropeptide Y, but the inhibitory or excitatory nature of them is unknown. However, counts of all hippocampal cells immunoreactive for glutamic acid decarboxylase showed that the GABA interneurons survive ischemia. It is therefore suggested that the vulnerable interneurons in hilus and the mossy fiber layer do not contain GABA. As the GABA interneurons, other hippocampal interneurons also survive ischemia. Among these, the CA1 and CA3 interneurons containing neuropeptide Y demonstrate permanently reduced immunoreactivity for neuropeptide Y, evident 1-2 days after ischemia. Another subpopulation transiently shows a decrease in immunoreactivity for parvalbumin approximately 4 days after ischemia. These results are in contrast to the finding that protein synthesis in hippocampal interneurons returns to preischemic levels 9 hours after ischemia. The integrity between excitation and inhibition in CA1 is unchanged in hippocampal slices taken from animals 1-2 days after ischemia. Furthermore, GABA can readily be released upon potassium stimulation in the period preceding CA1 pyramidal cell death. Binding to hippocampal benzodiazepine sites, however, declines prior to ischemic CA1 pyramidal cell death. It is demonstrated that administration of diazepam and GABA uptake inhibitors during this period offers postischemic neuron protection in CA1. There is no conclusive evidence of excitatory hyperactivity preceding ischemic CA1 pyramidal cell death. On the contrary, results from Chang et al. (1) suggest that ischemic loss of interneurons in the dentate hilus is associated with an increase in inhibition. However, it is suggested that GABA inhibition is insufficient to counterbalance the detrimental process during normal or even reduced postischemic excitation, since drugs believed to increase GABA inhibition reduce ischemic cell death. The early and permanent reduction in neuropeptide Y immunoreactivity may reflect a reduced capacity of these interneurons to release neuropeptide Y and thereby reduce presynaptic glutamate release.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Morphology of midlumbar interneurones relaying information from group II muscle afferents in the cat spinal cord.

The morphology of midlumbar interneurones with peripheral input from group II muscle afferents was analysed after intracellular injection of horseradish peroxidase (HRP). Twenty-three interneurones were stained intrasomatically and five others intra-axonally. The majority (10 of 13) of interneurones located in lamina VII (intermediate zone and ventral horn interneurones) were found to project ipsilaterally. They had medium-sized somata and dendrites projecting radially over a distance of more than 1 mm. All of these neurones had axons that projected caudally within the ventral part of the lateral funiculus or in the lateral part of the ventral funiculus, although four had in addition an ascending secondary axonal branch. Numerous axon collaterals were given off from these axons, both before and after they left the grey matter. The collaterals arborized within laminae VII, VIII, and IX, where they covered the area of several motor nuclei. Intra-axonal labelling of five neurones with similar input and axon trajectories revealed several axon collaterals given off between the cell body and the terminal projection areas in L7 or S1 segments. Only three of the labelled interneurones located in lamina VII and displaying the same kind of input had axons with different destinations; their axons crossed to the opposite side of the spinal cord and ascended within the contralateral ventral funiculus. These were large neurones with extensive dendritic trees, which had fairly thick axons with initial axon collaterals that branched primarily ipsilaterally (within laminae V-VIII). Interneurones located in lamina V and in the bordering parts of laminae IV and VI (dorsal horn interneurones; n = 10) constituted a very nonhomogenous population. They projected either ipsilaterally or contralaterally and had either ascending or descending axons running in either the lateral or ventral funiculi. Generally, dorsal horn interneurones had cell bodies smaller than those of intermediate zone and ventral horn interneurones, and their dendrites extended less extensively and less uniformly around the soma. Their initial axon collaterals branched primarily in the dorsal horn, or in lamina VII, but not in or close to the motor nuclei. Our results support the conclusions of previous physiological studies that the intermediate zone and ventral horn midlumbar interneurones with group II input and that project to motor nuclei have collateral actions on other interneurones in the L4-L6 segments, and that dorsal horn interneurones do not project to motoneurones, but have as their targets other interneurones or ascending cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Role of local nonspiking interneurons in the generation of rhythmic motor activity in the stick insect.

Local nonspiking interneurons in the thoracic ganglia of insects are important premotor elements in posture control and locomotion. It was investigated whether these interneurons are involved in the central neuronal circuits generating the oscillatory motor output of the leg muscle system during rhythmic motor activity. Intracellular recordings from premotor nonspiking interneurons were made in the isolated and completely deafferented mesothoracic ganglion of the stick insect in preparations exhibiting rhythmic motor activity induced by the muscarinic agonist pilocarpine. All interneurons investigated provided synaptic drive to one or more motoneuron pools supplying the three proximal leg joints, that is, the thoraco-coxal joint, the coxa-trochanteral joint and the femur-tibia joint. During rhythmicity in 83% (n = 67) of the recorded interneurons, three different kinds of synaptic oscillations in membrane potential were observed: (1) Oscillations were closely correlated with the activity of motoneuron pools affected; (2) membrane potential oscillations reflected only certain aspects of motoneuronal rhythmicity; and (3) membrane potential oscillations were correlated mainly with the occurrence of spontaneous recurrent patterns (SRP) of activity in the motoneuron pools. In individual interneurons membrane potential oscillations were associated with phase-dependent changes in the neuron's membrane conductance. Artificial changes in the interneurons' membrane potential strongly influenced motor activity. Injecting current pulses into individual interneurons caused a reset of rhythmicity in motoneurons. Furthermore, current injection into interneurons influenced shape and probability of occurrence for SRPs. Among others, identified nonspiking interneurons that are involved in posture control of leg joints were found to exhibit the above properties. From these results, the following conclusions on the role of nonspiking interneurons in the generation of rhythmic motor activity, and thus potentially also during locomotion, emerge: (1) During rhythmic motor activity most nonspiking interneurons receive strong synaptic drive from central rhythm-generating networks; and (2) individual nonspiking interneurons some of which underlie sensory-motor pathways in posture control, are elements of central neuronal networks that generate alternating activity in antagonistic leg motoneuron pools.

Action Potentials↗
PubMed2005

Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin.

We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV- and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV- and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can prevent the damage of interneurons in the hippocampus after cerebral ischemia. Thus, our study provides valuable information for the pathogenesis after cerebral ischemia.

Animals↗
PubMed2002

Early sequential formation of functional GABA(A) and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus.

During postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch-clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin-filled neurons. At P0, three types of interneurons were found: (i) non-innervated "silent" interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABA(A) synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non-innervated neurons and interneurons with GABA(A) and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18-20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA-glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.

Animals↗
PubMed1997

Interneuron-specific Ca2+ responses linked to metabotropic and ionotropic glutamate receptors in rat hippocampal slices.

Glutamate-mediated regulation of intracellular Ca2+ levels was examined in different populations of CA1 interneurons, using confocal microscopy and the Ca2+ indicator fluo 3-AM in rat hippocampal slices. Interneurons in basal [stratum oriens/alveus (OA)] and apical [strata radiatum and lacunosum-moleculare (R/LM)] dendritic layers responded heterogeneously to glutamate. In control medium, OA interneurons responded mostly with oscillatory Ca2+ responses, which consisted of a large Ca2+ transient and successive smaller elevations. R/LM interneurons responded mostly with biphasic responses, characterized by an initial large transient and a secondary prolonged elevation. Other interneurons in both R/LM and OA responded with transient elevations in Ca2+ levels. Ionotropic glutamate receptor antagonists (+/-)2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitro-quinoxaline-2,3-dione reduced peak Ca2+ responses in OA and R/LM cells, and blocked biphasic responses in R/LM interneurons. The metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine reduced peak Ca2+ responses only in OA interneurons, and prevented oscillatory responses. In low Ca2+ medium, peak responses were reduced in R/LM but not in OA interneurons, and oscillatory responses were absent. Combination of ionotropic and metabotropic receptor antagonists blocked all glutamate-evoked Ca2+ responses. Activation of different types of glutamate receptors may thus produce heterogeneous Ca2+ signals in subpopulations of CA1 interneurons. Ionotropic receptors may generate biphasic responses in interneurons in apical dendritic layers, whereas combined activation of metabotropic and ionotropic receptors may trigger oscillatory responses in interneurons of basal dendritic layers. These heterogeneous Ca2+ responses indicate that glutamate-mediated Ca2+ processes and second messenger systems differ in subpopulations of hippocampal interneurons and suggest possible postsynaptic functional specialization of interneurons.

Animals↗
PubMed1987

An interneuronal relay for group I and II muscle afferents in the midlumbar segments of the cat spinal cord.

1. The properties of interneurones located in the 4th lumbar segment of the cat spinal cord (L4 interneurones) have been investigated by intracellular and extracellular recording from individual neurones. The study focused on interneurones projecting to hind-limb motor nuclei and/or interposed in pathways from group II muscle afferents. The projection to motor nuclei was assessed from antidromic activation of the neurones by stimuli applied in the motor nuclei of the 7th lumbar (L7) segment. 2. Interneurones which projected to gastrocnemius-soleus or hamstring motor nuclei were found in laminae VI and VII and at the border between laminae VII and VIII. The dominant peripheral input to most of them was from group II muscle afferents, but they were also influenced by group I muscle afferents and by afferents in cutaneous, joint and interosseous nerves. Both excitatory post-synaptic potentials (e.p.s.p.s) and inhibitory post-synaptic potentials (i.p.s.p.s) were evoked from all of these fibre systems. 3. The same kind of multimodal input was also found in other interneurones in laminae VI and VII. However, their axonal projections were not identified and they might have included neurones projecting to motor nuclei (though outside the areas which were stimulated) as well as neurones with more local actions. 4. Interneurones located in laminae IV and V of the dorsal horn appeared to constitute a separate functional population since both their projections and their input differed from those of the more ventrally located interneurones; none of the dorsal horn interneurones were found to project to motor nuclei and none had input from group I afferents, although they were influenced by group II muscle afferents and by afferents in cutaneous, joint and interosseous nerves. 5. Many of the excitatory actions from group I and II afferents upon L4 interneurones were found to be evoked monosynaptically. A high proportion of L4 neurones synapsing upon motoneurones would thus be interposed in disynaptic reflex pathways from these afferents. In comparison to actions evoked via interneurones of the caudal lumbar segments, any post-synaptic potentials (p.s.p.s) evoked via L4 interneurones would be delayed. These delays would amount to 0.4-0.9 ms for p.s.p.s. from group I afferents and by 0.5-2.5 ms for group II p.s.p.s. 6. In many interneurones, particularly those located ventrally, i.p.s.p.s. were evoked by group I and II muscle afferents at latencies which indicated that they were evoked disynaptically. They may therefore reflect inhibitory interactions between subpopulations of L4 interneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1993

Axonal projections and synaptic connections of C5 segment expiratory interneurones in the cat.

1. Respiratory interneurones in the C4-C6 segments of the spinal cord have only recently been described; until now their projections and connections were not known. We investigated expiratory interneurones in the C5 spinal segment, using antidromic mapping to trace their projections and spike-triggered averaging to test their synaptic connections with phrenic motoneurones. 2. A total of seventy expiratory interneurones were recorded in nineteen cats anaesthetized with pentobarbitone, paralysed and ventilated. The interneurones were found scattered dorsomedial to the phrenic motor nucleus, with discharge patterns of a constant (66%), augmenting (24%) or decrementing (10%) type. 3. Interneurone axons were found in the ipsilateral ventrolateral funiculus using antidromic activation at thresholds < 20 microA. The axons of eighteen of thirty-three interneurones tested (55%) were found to extend to the rostral part of the C6 segment, seventeen of thirty-three (52%) to the caudal part of the C6 segment and ten of nineteen (53%) to the rostral part of the C7 segment. 4. Axon collaterals for thirteen of thirty-three interneurones (39%) were found in the ipsilateral half of the C6 segment, with their endings near the phrenic motor nucleus. In three cases two collaterals were found. None of the interneurones had projections in the contralateral halves of the C5 or C6 segments. 5. In a separate group of thirty-four expiratory interneurones, antidromic mapping was used to find an axon collateral in the C6 segment prior to spike-triggered averaging. Eleven of these interneurones had collaterals (32%) and were subsequently tested for synaptic connections to thirty-two phrenic motoneurones. In three separate instances (9%), inhibitory postsynaptic potentials were observed. Amplitudes, fall times and half-amplitude widths of the inhibitory postsynaptic potentials were 6.7, 10.4 and 10.6 microV; 0.3, 0.5 and 0.7 ms and 0.6, 1.6 and 3.3 ms respectively. 6. We conclude: (i) there is a population of expiratory interneurones in the C5 segment, located predominantly dorsomedial to the phrenic motor nucleus; (ii) at least one-half of these interneurones have ipsilateral intersegmental projections to the C6 segment and (iii) although synaptic connections from expiratory interneurones in the C5 segment to phrenic motoneurones in the C6 segment may be rare, the observed inhibitory postsynaptic potentials had fall times and latencies commensurate with monosynaptic connections.

Animals↗
PubMed2002

Modulation of network behaviour by changes in variance in interneuronal properties.

Interneurones are important regulators of neuronal networks. The conventional approach to interneurones is to focus on the mean values of various parameters. Here we tested the hypothesis that changes in the variance of interneuronal properties (e.g. in the degree of scattering of parameter values of individual cells around the population mean) may modify the behaviour of networks. Biophysically based multicompartmental models of principal cells and interneurones showed that changes in the variance in the electrophysiological and anatomical properties of interneurones significantly alter the input-output functions, rhythmicity and synchrony of principal cells, even if the mean values were unchanged. In most cases, increased heterogeneity in interneurones resulted in stronger inhibition of principal cell firing; however, there were parameter ranges where increased interneuronal variance decreased the inhibition of principal cells. Electrophysiological recordings showed that the variance in the resting membrane potential of CA1 stratum oriens interneurones persistently increased following experimental complex febrile seizures in developing rats, without a change in the mean resting membrane potential, indicating that lasting alterations in interneuronal heterogeneity can take place in real neuronal systems. These computational and experimental data demonstrate that modifications in interneuronal population variance influence the behaviour of neuronal networks, and suggest a physiological role for interneuronal diversity. Furthermore, the results indicate that interneuronal heterogeneity can change in neurological diseases, and raise the possibility that neuromodulators may act by regulating the variance of key parameters in interneuronal populations.

Animals↗
PubMed2006

Hybrid systems analysis of the control of burst duration by low-voltage-activated calcium current in leech heart interneurons.

The leech heartbeat CPG is paced by the alternating bursting of pairs of mutually inhibitory heart interneurons that form elemental half-center oscillators. We explore the control of burst duration in heart interneurons using a hybrid system, where a living, pharmacologically isolated, heart interneuron is connected with artificial synapses to a model heart interneuron running in real-time, by focusing on a low-voltage-activated (LVA) calcium current I(CaS). The transition from silence to bursting in this half-center oscillator occurs when the spike frequency of the bursting interneuron declines to a critical level, f(Final), at which the inhibited interneuron escapes owing to a build-up of the hyperpolarization-activated cation current, I(h). We varied I(CaS) inactivation time constant either in the living heart interneuron or in the model heart interneuron. In both cases, varying I(CaS) inactivation time constant did not affect f(Final) of either interneuron, but in the varied interneuron, the time constant of decline of spike frequency during bursts to f(Final) and thus the burst duration varied directly and nearly linearly with I(CaS) inactivation time constant. Bursts of the opposite, nonvaried interneuron did not change. We show also that control of burst duration by I(CaS) inactivation does not require synaptic interaction by reconstituting autonomous bursting in synaptically isolated living interneurons with injected I(CaS). Therefore inactivation of LVA calcium current is critically important for setting burst duration and thus period in a heart interneuron half-center oscillator and is potentially a general intrinsic mechanism for regulating burst duration in neurons.

Algorithms↗
PubMed1975

Nonspiking interneurons in walking system of the cockroach.

Intracellular recordings were made from the neurites of interneurons and motoneurons in the metathoracic ganglion of the cockroach, Periplaneta americana. Many neurons were penetrated which failed to produce action potentials on the application of large depolarizing currents. Nevertheless, some of them strongly excited and/or inhibited slow motoneurons innervating leg musculature, even with weak depolariziing musculature, even with weak depolarizing currents. Cobalt-sulfide-straining of these nonspiking neurons showed them to be interneurons with their neurites contained entirely within the metathoracic ganglion. Two further characteristics of these interneurons were rapid spontaneous fluctuations in membrane potential and a low resting membrane potential. One nonspiking neuron, interneuron I, when depolarized caused a strong excitation of the set of slow levator motoneurons which discharge in bursts during stepping movements of the metathoracic leg. During rhythmic leg movements the membrane potential of interneuron I oscillated with the depolarizing phases occurring at the same time as bursts of activity in the levator motorneurons. No spiking or any other nonspiking neuron was penetrated which could excite these levator motoneurons. From all these observations we conclude that oscillations in the membrane potential of interneuron I are entirely responsible for producing the levator bursts, and thus for producing stepping movements in a walking animal. During rhythmic leg movements, bursts of activity in levator and depressor motoneurons are initiated by slow graded depolarizations. The similarity of the synaptic activity in these two types of motoneurons suggests that burst activity in the depressor motoneurons is also produced by rhythmic activity in nonspiking interneurons. The fact that no spiking neuron was found to excite the depressor motoneurons supports this conclusion. Interneuron I is also an element of the rhythm-generating system, since short depolarizing pulses applied to it during rhythmic activity could reset the thythm. Long-duration current pulses applied to interneuron I in a quiescent animal did not produce rhythmic activity. This observation, together with the finding that during rhythmic activity the slow depolarizations in interneuron I are usually terminated by IPSPs, suggests that interneuron I alone does not generate the rhythm. No spiking interneurons have yet been enccountered which influence the activity in levator motoneurons. Thus, we conclude that the rhythm is generated in a network of nonspiking interneurons. The cellular mechanisms for generating the oscillations in this network are unknown. Continued.

Action Potentials↗