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PubMed1991

Octopaminergic modulation of interneurons in the flight system of the locust.

1. Modulatory effects of octopamine perfusion on identified central neurons in the flight system of the locust Locusta migratoria were examined by means of intracellular recordings from the isolated metathoracic ganglion. 2. Octopamine increased the excitatory response of elevator motoneurons to electrical stimulation of the hindwing tegula and increased the probability of triggering rhythmic activity in the flight system by current injection into single interneurons. 3. These effects of octopamine on the flight system are due in part to octopamine inducing intrinsic bursting properties in flight interneurons. Plateau potentials were evoked in these interneurons by synaptic input from tegula or by the injection of depolarizing current pulses. These potentials were prematurely terminated by hyperpolarizing currents, and their generation was voltage sensitive in that they were suppressed with hyperpolarizing offset currents. 4. Longer depolarizing current pulses evoked endogenous bursting in a number of flight interneurons. This rhythmic bursting was reset by the injection of pulses of hyperpolarizing currents. The frequency of bursting was dependent on the injected current strength. 5. The injection of hyperpolarizing current into flight interneurons during octopamine-induced rhythmic activity lead to sudden decreases in the amplitude of the depolarizations thus indicating that plateau potentials contribute to the generation of the rhythmic depolarizations. 6. The shape of the depolarizations, the duration of the bursts (50-75 ms), and the frequency range of endogenous bursting (4-16 Hz) as seen in individual interneurons during octopamine perfusion were similar to the corresponding characteristics in the same neurons during wind-induced flight activity in deafferented locusts. This correspondence suggests that intrinsic bursting properties may play an important role in generating the normal motor pattern for flight.

Animals↗

PubMed1991

Discharge patterns of trigeminal commissural last-order interneurons during fictive mastication in the rabbit.

1. The aim of these experiments was to examine the physiological properties and patterns of firing of trigeminal interneurons during fictive mastication in anesthetized and paralyzed rabbits. Antidromic stimulation was used to show that the 82 interneurons projected to the area of the contralateral fifth nerve motor nucleus (NVmot). 2. Straight-line conduction velocities calculated from stereotaxic coordinates of the stimulating and recording electrodes for 63 interneurons were found to range between 3.7 and 16.3 m/s (mean, 9.5 m/s). 3. Histological reconstructions of recording electrode tracks showed that the interneurons observed in this study were located in the lateral brain stem in or just medial to the rostral trigeminal sensory nuclei, including the intertrigeminal (NVint) and supratrigeminal (NVs) areas, the main sensory nucleus of the fifth nerve (NVsnpr), the rostral subdivision of the oral nucleus of the spinal trigeminal tract (NVor tau), and the rostral part of the parvocellular reticular nucleus (NRpc alpha). 4. Forty-six interneurons were shown to have low-threshold (LT) peripheral receptive fields, and 41 of these (88%) were in the oral cavity. Most of the responses were rapidly adapting. 5. Twenty-eight interneurons changed their pattern of firing during cortically induced fictive mastication. The discharge frequency of 20 neurons varied in phase with the fictive masticatory motor output, which was recorded from central ends of cut hypoglossal nerves (XII) and/or from the NVmot. Others were briefly excited and then inhibited (n = 2), only inhibited (n = 4), or tonically excited during fictive mastication (n = 2). Fifteen others were unaffected by this test. 6. It was found that the rhythmically active neurons could be further subdivided into two categories: those receiving short-latency excitatory input from the masticatory area of the cortex (n = 11) and those that did not (n = 9). No obvious differences in peripheral receptive fields for neurons in these categories were found. 7. We suggest that these phasically active premotor neurons are part of the circuitry generating the rhythmic masticatory pattern, specifically those that directly control the bursts of firing of the trigeminal motoneurons (burst generators, BGs). Their properties allow them to integrate sensory information and descending commands with the masticatory rhythm that is probably generated in midline brainstem reticular nuclei.

Animals↗

PubMed1995

Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors.

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Recruitment of GABAergic inhibition and synchronization of inhibitory interneurons in rat neocortex.

Intracellular recordings were obtained from pyramidal and interneuronal cells in rat neocortical slices to examine the recruitment of GABAergic inhibition and inhibitory interneurons. In the presence of the convulsant agent 4-aminopyridine (4-AP), after excitatory amino acid (EAA) ionotropic transmission was blocked, large-amplitude triphasic inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 10-40 s) and synchronously in pyramidal neurons. After exposure to the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist picrotoxin, large-amplitude monophasic slow IPSPs persisted in these cells. In the presence of 4-AP and EAA blockers, interneurons showed periodic spike firing. Although some spikes rode on an underlying synaptic depolarization, much of the rhythmic firing consisted of spikes having highly variable amplitudes, arising abruptly from baseline, even during hyperpolarization. The spike firing and depolarizing synaptic potentials were completely suppressed by picrotoxin exposure, although monophasic slow IPSPs persisted in interneurons. This suggests that this subset of interneurons may participate in generating fast GABA(A) IPSPs, but not slow GABA(B) IPSPs. Cell morphology was confirmed by intracellular injection of neurobiotin or the fluorescent dye Lucifer yellow CH. Dye injection into interneurons often (>70%) resulted in the labeling of two to six cells (dye coupling). These findings suggest that GABA(A)ergic neurons may be synchronized via recurrent collaterals through the depolarizing action of synaptically activated GABA(A) receptors and a mechanism involving electrotonic coupling. Although inhibitory neurons mediating GABA(B) IPSPs may be entrained by the excitatory GABA(A) mechanism, they appear to be a separate subset of GABAergic neurons capable of functioning independently with autonomous pacing.

Animals↗

PubMed1997

Glutamatergic N2v cells are central pattern generator interneurons of the lymnaea feeding system: new model for rhythm generation.

We aimed to show that the paired N2v (N2 ventral) plateauing cells of the buccal ganglia are important central pattern generator (CPG) interneurons of the Lymnaea feeding system. N2v plateauing is phase-locked to the rest of the CPG network in a slow oscillator (SO)-driven fictive feeding rhythm. The phase of the rhythm is reset by artificially evoked N2v bursts, a characteristic of CPG neurons. N2v cells have extensive input and output synaptic connections with the rest of the CPG network and the modulatory SO cell and cerebral giant cells (CGCs). Synaptic input from the protraction phase interneurons N1M (excitatory), N1L (inhibitory), and SO (inhibitory-excitatory) are likely to contribute to a ramp-shaped prepotential that triggers the N2v plateau. The prepotential has a highly complex waveform due to progressive changes in the amplitude of the component synaptic potentials. Most significant is the facilitation of the excitatory component of the SO --> N2v monosynaptic connection. None of the other CPG interneurons has the appropriate input synaptic connections to terminate the N2v plateaus. The modulatory function of acetylcholine (ACh), the transmitter of the SO and N1M/N1Ls, was examined. Focal application of ACh (50-ms pulses) onto the N2v cells reproduced the SO --> N2v biphasic synaptic response but also induced long-term plateauing (20-60 s). N2d cells show no endogenous ability to plateau, but this can be induced by focal applications of ACh. The N2v cells inhibit the N3 tonic (N3t) but not the N3 phasic (N3p) CPG interneurons. The N2v --> N3t inhibitory synaptic connection is important in timing N3t activity. The N3t cells recover from this inhibition and fire during the swallow phase of the feeding pattern. Feedback N2v inhibition to the SO, N1L protraction phase interneurons prevents them firing during the retraction phase of the feeding cycle. The N2v --> N1M synaptic connection was weak and only found in 50% of preparations. A weak N2v --> CGC inhibitory connection prevents the CGCs firing during the rasp (N2) phase of the feeding cycle. These data allowed a new model for the Lymnaea feeding CPG to be proposed. This emphasizes that each of the six types of CPG interneuron has a unique set of synaptic connections, all of which contribute to the generation of a full CPG pattern.

Acetylcholine↗

PubMed1998

Response patterns and force relations of monkey spinal interneurons during active wrist movement.

The activity of C6-T1 spinal cord neurons was recorded in three macaques while they generated isometric wrist flexion and extension torques in visually guided step-tracking tasks. Electromyographic activity (EMG) was recorded in </=12 independent forearm muscles. Spike-triggered averages (STAs) of rectified and unrectified EMG were used to classify neurons into four groups. Motoneurons (MNs) had a clear postspike motor unit signature in the unrectified STA of one muscle. Premotor interneurons (PreM-INs) had postspike effects in at least one muscle, with onset latencies of >/=3.5 ms from the trigger. Synchrony interneurons (Sy-INs) were non-PreM-Ins that had spike-related features with latencies <3.5 ms in at least one muscle. Unidentified interneurons (U-INs) showed no features in any of the STAs. A total of 572 task-related spinal neurons were studied; 29 cells were MNs, 97 PreM-INs, 32 Sy-INs, and 414 U-INs. MNs were activated predominantly in a tonic fashion during the ramp-and-hold torques and were active in one direction only. The most common response pattern for interneurons, irrespective of their class, was phasic-tonic activity, followed by purely tonic and purely phasic activity. Most interneurons (77%) were bidirectionally active in both flexion and extension. For all classes of interneurons, units with phasic response components tended to be activated first, before torque onset, followed by tonic units. The onset times of PreM-INs relative to onsets of their target muscles were distributed broadly, with a mean of -25 +/- 128 (SD) ms. For most neurons with tonic response components (all MNs, 71% of PreM-INs, 67% of Sy-INs, and 84% of U-INs), activity during the hold period was correlated significantly with the magnitude of static torque exerted by the monkey. The rate-torque regressions generally had positive slopes with higher mean slopes for extension than for flexion. The phasic response components were correlated significantly with rate of change of torque for a smaller percentage of tested PreM-Ins (50%), Sy-INs (83%), and U-INs (77%). In contrast to other premotor neurons [corticomotoneuronal (CM), rubromotoneuronal (RM), and dorsal root ganglion (DRG) afferents] previously characterized under similar conditions, a larger proportion of the spinal PreM-INs were activated after onset of their target muscles, probably reflecting a larger proportion of PreM-INs driven by peripheral input. The rate-torque slopes of PreM-INs tended to be less steep than those of CM and RM cells. Unlike the CM and DRG PreM afferents, which were activated unidirectionally, most spinal PreM-INs showed bidirectional activity, like RM cells.

Action Potentials↗

PubMed1999

Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord.

Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. To test the necessity of spinal commissural interneurons in the generation of the swim rhythm in lamprey, longitudinal midline cuts of the isolated spinal cord preparation were made. Fictive swimming was then induced by bath perfusion with an excitatory amino acid while recording ventral root activity. When the spinal cord preparation was cut completely along the midline into two lateral hemicords, the rhythmic activity of fictive swimming was lost, usually replaced with continuous ventral root spiking. The loss of the fictive swim rhythm was not due to nonspecific damage produced by the cut because rhythmic activity was present in split regions of spinal cord when the split region was still attached to intact cord. The quality of this persistent rhythmic activity, quantified with an autocorrelation method, declined with the distance of the split spinal segment from the remaining intact spinal cord. The deterioration of the rhythm was characterized by a lengthening of burst durations and a shortening of the interburst silent phases. This pattern of deterioration suggests a loss of rhythmic inhibitory inputs. The same pattern of rhythm deterioration was seen in preparations with the rostral end of the spinal cord cut compared with those with the caudal end cut. The results of this study indicate that commissural interneurons are necessary for the generation of the swimming rhythm in the lamprey spinal cord, and the characteristic loss of the silent interburst phases of the swimming rhythm is consistent with a loss of inhibitory commissural interneurons. The results also suggest that both descending and ascending commissural interneurons are important in the generation of the swimming rhythm. The swim rhythm that persists in the split cord while still attached to an intact portion of spinal cord is thus imposed by interneurons projecting from the intact region of cord into the split region. These projections are functionally short because rhythmic activity was lost within approximately five spinal segments from the intact region of spinal cord.

Animals↗

PubMed2002

Endogenous and network properties of Lymnaea feeding central pattern generator interneurons.

Understanding central pattern generator (CPG) circuits requires a detailed knowledge of the intrinsic cellular properties of the constituent neurons. These properties are poorly understood in most CPGs because of the complexity resulting from interactions with other neurons of the circuit. This is also the case in the feeding network of the snail, Lymnaea, one of the best-characterized CPG networks. We addressed this problem by isolating the interneurons comprising the feeding CPG in cell culture, which enabled us to study their basic intrinsic electrical and pharmacological cellular properties without interference from other network components. These results were then related to the activity patterns of the neurons in the intact feeding network. The most striking finding was the intrinsic generation of plateau potentials by medial N1 (N1M) interneurons. This property is probably critical for rhythm generation in the whole feeding circuit because the N1M interneurons are known to play a pivotal role in the initiation of feeding cycles in response to food. Plateau potential generation in another cell type, the ventral N2 (N2v), appeared to be conditional on the presence of acetylcholine. Examination of the other isolated feeding CPG interneurons [lateral N1 (N1L), dorsal N2 (N2d), phasic N3 (N3p)] and the modulatory slow oscillator (SO) revealed no significant intrinsic properties in relation to pattern generation. Instead, their firing patterns in the circuit appear to be determined largely by cholinergic and glutamatergic synaptic inputs from other CPG interneurons, which were mimicked in culture by application of these transmitters. This is an example of a CPG system where the initiation of each cycle appears to be determined by the intrinsic properties of a key interneuron, N1M, but most other features of the rhythm are probably determined by network interactions.

Acetylcholine↗

PubMed2006

Regulation of cortical interneurons by neurotrophins: from development to cognitive disorders.

Parvalbumin-positive interneurons, which include basket and chandelier cells, represent a unique class of interneurons. By innervating the soma and the axonal initial segment of pyramidal cells, these interneurons can elicit powerful control on the output of pyramidal cells and consequently are important for a number of physiological processes in the mammalian brain. Recent evidence indicates that neurotrophins regulate the development and functions of parvalbumin-positive interneurons. Disruption of neurotrophin-mediated regulation of interneurons is thought to contribute to the pathological processes underlying CNS dysfunction. This review brings together recently described roles of neurotrophins in migration, differentiation, synaptogenesis during development, and acute effects of neurotrophins in transmission at inhibitory synapses, Cl(-) homeostasis, and network activity of cortical interneurons. The authors also discuss the importance of neurotrophin regulation of GABAergic neurons in schizophrenia and epilepsy.

Animals↗

PubMed2005

Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon.

Fate determination in the mammalian forebrain, where mature phenotypes are often not achieved until postnatal stages of development, has been an elusive topic of study despite its relevance to neuropsychiatric disease. In the ventral telencephalon, major subgroups of cerebral cortical interneurons originate in the medial ganglionic eminence (MGE), where the signaling molecule sonic hedgehog (Shh) continues to be expressed during the period of neuronogenesis. To examine whether Shh regulates cortical interneuron specification, we studied mice harboring conditional mutations in Shh within the neural tube. At embryonic day 12.5, NestinCre:Shh(Fl/Fl) mutants have a relatively normal index of S-phase cells in the MGE, but many of these cells do not co-express the interneuron fate-determining gene Nkx2.1. This effect is reproduced by inhibiting Shh signaling in slice cultures, and the effect can be rescued in NestinCre:Shh(Fl/Fl) slices by the addition of exogenous Shh. By culturing MGE progenitors on a cortical feeder layer, cell fate analyses suggest that Shh signaling maintains Nkx2.1 expression and cortical interneuron fate determination by MGE progenitors. These results are corroborated by the examination of NestinCre:Shh(Fl/Fl) cortex at postnatal day 12, in which there is a dramatic reduction in cell profiles that express somatostatin or parvalbumin. By contrast, analyses of Dlx5/6Cre:Smoothened(Fl/Fl) mutant mice suggest that cell-autonomous hedgehog signaling is not crucial to the migration or differentiation of most cortical interneurons. These results combine in vitro and ex vivo analyses to link embryonic abnormalities in Shh signaling to postnatal alterations in cortical interneuron composition.

Animals↗

PubMed1975

Co-ordinating interneurones of the locust which convey two patterns of motor commands: their connexions with ventilatory motoneurones.

1. The interneurones which make widespread connexions with flight motoneurones also synapse upon ventilatory motoneurones so that in all 50 motoneurones receive synapses. They influence three aspects of ventilation; (a) the closing and opening movements of the thoracic spiracles, (b) some aspects of abdominal pumping movements and (c) the recruitment of some motoneurones controlling head pumping. 2. The two closer motoneurones of a particular thoracic spiracle receive the same excitatory synaptic inputs (EPSPs) during expiration. The EPSPs match those in appropriate flight motoneurones. 3. The closer motoneurones of each thoracic spiracle whose somata are in the pro-, meso- or metathoracic ganglia all receive the same excitatory synaptic inputs. These inputs are an adequate explanation of the pattern of spikes in the closer motoneurones. Both the slow ventilatory and fast rhythms of synaptic potentials are expressed as spikes; the slow as the overall expiratory burst of spikes and the fast as the groups of spikes within that burst. This establishes a ventilatory function for the interneurones. All thoracic closer motoneurones therefore receive the same excitatory commands which will tend to synchronize the movements of each spiracle. 4. Spiracular opener motoneurones are inhibited during expiration, their IPSPs matching the EPSPs in flight or closer motoneurones. Therefore the interneurones have reciprocal effects on the antagonistic motoneurones of the spiracles. 5. The interneurones synapse upon some motoneurones which control the pumping movements of the abdomen and which have their somata in the metathoracic or first unfused abdominal ganglion. Motoneurones in four separate ganglia therefore receive inputs from these interneurones. 6. The interneurones also synapse upon motoneurones which control an auxiliary form of ventilation, head pumping.

Action Potentials↗

PubMed2006

Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal cortex in a model of temporal lobe epilepsy.

Temporal lobe epilepsy is the most common type of epilepsy in adults, and its pathophysiology remains unclear. Layer II stellate cells of the entorhinal cortex, which are hyperexcitable in animal models of temporal lobe epilepsy, provide the predominant synaptic input to the hippocampal dentate gyrus. Previous studies have ascribed the hyperexcitability of layer II stellate cells to GABAergic interneurons becoming "dormant" after disconnection from their excitatory synaptic inputs, which has been reported to occur during preferential loss of layer III pyramidal cells. We used whole-cell recording from slices of entorhinal cortex in pilocarpine-treated epileptic rats to test the dormant interneuron hypothesis. Hyperexcitability appeared as multiple action potentials and prolonged depolarizations evoked in layer II stellate cells of epileptic rats but not controls. However, blockade of glutamatergic synaptic transmission caused similar percentage reductions in the frequency of spontaneous IPSCs in layer II stellate cells of control and epileptic rats, suggesting similar levels of excitatory synaptic input to GABAergic interneurons. Direct recordings and biocytin labeling revealed two major types of interneurons in layer III whose excitatory synaptic drive in epileptic animals was undiminished. Interneurons in layer III did not appear to be dormant; therefore, we tested whether loss of GABAergic synapses might underlie hyperexcitability of layer II stellate cells. Stereological evidence of fewer GABAergic interneurons, fewer gephyrin-immunoreactive punctae, and reduced frequency of spontaneous IPSCs and miniature IPSCs (recorded in tetrodotoxin) confirmed that layer II stellate cell hyperexcitability is attributable, at least in part, to reduced inhibitory synaptic input.

Action Potentials↗

PubMed2005

Gap-junctional coupling between neurogliaform cells and various interneuron types in the neocortex.

Electrical synapses contribute to the generation of synchronous activity in neuronal networks. Several types of cortical GABAergic neurons acting via postsynaptic GABA(A) receptors also form electrical synapses with interneurons of the same class, suggesting that synchronization through gap junctions could be limited to homogenous interneuron populations. Neurogliaform cells elicit combined GABA(A) and GABA(B) receptor-mediated postsynaptic responses in cortical pyramidal cells, but it is not clear whether neurogliaform cells are involved in networks linked by electrical coupling. We recorded from pairs, triplets, and quadruplets of cortical neurons in layers 2 and 3 of rat somatosensory cortex (postnatal day 20-35). Neurogliaform cells eliciting slow IPSPs on pyramidal cells also triggered divergent electrical coupling potentials on interneurons. Neurogliaform cells were electrically coupled to other neurogliaform cells, basket cells, regular-spiking nonpyramidal cells, to an axoaxonic cell, and to various unclassified interneurons showing diverse firing patterns and morphology. Electrical interactions were mediated by one or two electron microscopically verified gap junctions linking the somatodendritic domain of the coupled cells. Our results suggest that neurogliaform cells have a unique position in the cortical circuit. Apart from eliciting combined GABA(A) and GABA(B) receptor-mediated inhibition on pyramidal cells, neurogliaform cells establish electrical synapses and link multiple networks formed by gap junctions restricted to a particular class of interneuron. Widespread electrical connections might enable neurogliaform cells to monitor the activity of different interneurons acting on GABA(A) receptors at various regions of target cells.

Action Potentials↗

PubMed2004

Primitive roles for inhibitory interneurons in developing frog spinal cord.

Understanding the neuronal networks in the mammal spinal cord is hampered by the diversity of neurons and their connections. The simpler networks in developing lower vertebrates may offer insights into basic organization. To investigate the function of spinal inhibitory interneurons in Xenopus tadpoles, paired whole-cell recordings were used. We show directly that one class of interneuron, with distinctive anatomy, produces glycinergic, negative feedback inhibition that can limit firing in motoneurons and interneurons of the central pattern generator during swimming. These same neurons also produce inhibitory gating of sensory pathways during swimming. This discovery raises the possibility that some classes of interneuron, with distinct functions later in development, may differentiate from an earlier class in which these functions are shared. Preliminary evidence suggests that these inhibitory interneurons express the transcription factor engrailed, supporting a probable homology with interneurons in developing zebrafish that also express engrailed and have very similar anatomy and functions.

Action Potentials↗

PubMed2005

Electrical coupling between interneurons with different excitable properties in the stratum lacunosum-moleculare of the juvenile CA1 rat hippocampus.

Electrical coupling among GABAergic interneurons is believed to play an essential role in shaping synchronized brain network activity related to cognition and behavior. We have studied the rules governing the electrical coupling between hippocampal interneurons located in stratum lacunosum-moleculare of the CA1 hippocampus. The most frequently recorded interneuron subtype had short multipolar dendrites and a dense local axonal arborization, typical of neurogliaform cells. Electrical excitability in this class of interneurons was heterogeneous. Although injection of small current steps evoked late spiking, larger steps triggered different types of firing patterns. Trains of action potentials ranged from clearly adapting to highly irregular, with clustered or mostly regular spikes. Electrotonic and action potentials could be propagated to the coupled cells; the coupling coefficient for electrotonic signals was 0.035, which compared with 0.005 for action potentials. Electrical coupling was reversibly blocked by application of carbenoxolone. Multiple simultaneous recordings indicated that interneurons with similar and different firing patterns were electrically coupled. This visual impression was quantitatively confirmed by principal component analysis applied to variables related to membrane excitability. In fact, the probability of finding electrically coupled neurons in our sample was not dependent on the excitable properties of the cells tested and was approximately 0.34. The presence of diffuse electrical coupling among hippocampal interneurons of stratum lacunosum-moleculare with different excitability is a novel finding with important implications. For example, the promiscuity of electrical connections may endow inhibitory networks with a large degree of flexibility and regulate the computational power of the hippocampus during different synchronized states.

Action Potentials↗

PubMed2004

Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors.

Anatomical studies have shown that the G-protein-coupled cannabinoid receptor-1 (CB1) is selectively expressed in a subset of GABAergic interneurons. It has been proposed that these cells regulate rhythmic activity and play a key role mediating the cognitive actions of marijuana and endogenous cannabinoids. However, the physiology, anatomy, and synaptic connectivity of neocortical CB1-expressing interneurons remain poorly studied. We identified a population of CB1-expressing interneurons in layer II/III in mouse neocortical slices. These cells were multipolar or bitufted, had a widely extending axon, and exhibited a characteristic pattern of irregular spiking (IS) in response to current injection. CB1-expressing-IS (CB1-IS) cells were inhibitory, establishing GABAA receptor-mediated synapses onto pyramidal cells and other CB1-IS cells. Recently, electrical coupling among other classes of cortical interneurons has been shown to contribute to the generation of rhythmic synchronous activity in the neocortex. We therefore tested whether CB1-IS interneurons are interconnected via electrical synapses using paired recordings. We found that 90% (19 of 21 pairs) of simultaneously recorded pairs of CB1-IS cells were electrically coupled. The average coupling coefficient was 6%. Signaling through electrical synapses promoted coordinated firing among CB1-IS cells. Together, our results identify a population of electrically coupled CB1-IS GABAergic interneurons in the neocortex that share a unique morphology and a characteristic pattern of irregular spiking in response to current injection. The synaptic interactions of these cells may play an important role mediating the cognitive actions of cannabinoids and regulating coherent neocortical activity.

Action Potentials↗

PubMed2004

Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons.

Clearance of extracellular glutamate is essential for limiting the activity of metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the relative contribution of transporters found in neuronal and glial membranes to this uptake is poorly understood. Hippocampal interneurons located at the oriens-alveus border express mGluR1alpha, a metabotropic glutamate receptor that regulates excitability and synaptic plasticity. To determine which glutamate transporters are essential for removing glutamate at these excitatory synapses, we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM) interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly depolarized to allow Ca2+ entry before stimulation. Selective inhibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihydrokainate increased the amplitude of these responses approximately threefold, indicating that these transporters compete with mGluRs for synaptically released glutamate. However, inhibition of all glutamate transporters with TBOA (DL-threo-b-benzyloxyaspartic acid) increased mGluR1 EPSCs >15-fold, indicating that additional transporters also shape activation of these receptors. To identify these transporters, we examined mGluR1 EPSCs in mice lacking GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for excitatory amino acid carrier; EAAT3). A comparison of responses recorded from wild-type and transporter knock-out mice revealed that the astroglial glutamate transporters GLT-1 and GLAST, but not the neuronal transporter EAAC1, restrict activation of mGluRs in O-LM interneurons. Transporter-dependent potentiation of mGluR1 EPSCs led to a dramatic increase in interneuron firing and enhanced inhibition of CA1 pyramidal neurons, suggesting that acute or prolonged disruption of transporter activity could lead to changes in network activity as a result of enhanced interneuron excitability.

Amino Acid Transport System X-AG↗

PubMed1999

Three GABA receptor-mediated postsynaptic potentials in interneurons in the rat lateral geniculate nucleus.

Inhibition is crucial for the thalamus to relay sensory information from the periphery to the cortex and to participate in thalamocortical oscillations. However, the properties of inhibitory synaptic events in interneurons are poorly defined because in part of the technical difficulty of obtaining stable recording from these small cells. With the whole-cell recording technique, we obtained stable recordings from local interneurons in the lateral geniculate nucleus and studied their inhibitory synaptic properties. We found that interneurons expressed three different types of GABA receptors: bicuculline-sensitive GABA(A) receptors, bicuculline-insensitive GABA(A) receptors, and GABA(B) receptors. The reversal potentials of GABA responses were estimated by polarizing the membrane potential. The GABA(A) receptor-mediated responses had a reversal potential of approximately -82 mV, consistent with mediation via Cl(-) channels. The reversal potential for the GABA(B) response was -97 mV, consistent with it being a K(+) conductance. The roles of these GABA receptors in postsynaptic responses were also examined in interneurons. Optic tract stimulation evoked a disynaptic IPSP that was mediated by all three types of GABA receptors and depended on activation of geniculate interneurons. Stimulation of the thalamic reticular nucleus evoked an IPSP, which appeared to be mediated exclusively by bicuculline-sensitive GABA(A) receptors and depended on the activation of reticular cells. The results indicate that geniculate interneurons form a complex neuronal circuitry with thalamocortical and reticular cells via feed-forward and feedback circuits, suggesting that they play a more important role in thalamic function than thought previously.

Animals↗