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At least 19 recordsLinked to original sources

PubMed1995

Modulation by adenosine of a neuronal inhibitory interaction in the rat hippocampus.

Adenosine is acknowledged to have a primarily inhibitory function in the central nervous system, but is believed to have little effect on inhibitory neurones themselves. It is, however, difficult to determine the effect of adenosine on inhibitory synaptic potentials since adenosine directly depresses evoked potentials and, in the presence of bicuculline to block GABAA-mediated inhibition, the bicuculline-resistant fraction of paired-pulse inhibition (ppi) is greater between pairs of small potentials than between pairs of larger potentials. Here, adenosine increased bicuculline-resistant ppi when stimulus strength was constant between adenosine and control but ppi of responses in adenosine was markedly less than ppi of control responses of the same size. Adenosine had less effect on the size of 'conditioned' potentials than on control potentials. It is concluded that adenosine can reduce the bicuculline-resistant fraction of paired-pulse inhibition in the hippocampus. Further quantitative comparison of the effects of adenosine on ppi and on single evoked potentials excluded a difference in the potency of adenosine at excitatory and inhibitory terminals as an explanation for this activity. The results suggest that adenosine may diminish bicuculline-resistant paired-pulse inhibition by enhancing a simultaneous facilitatory component of the neuronal responses.

Adenosine↗

PubMed1979

Projections of intestinal neurons showing immunoreactivity for vasoactive intestinal polypeptide are consistent with these neurons being the enteric inhibitory neurons.

Experiments were performed to determine if the distribution of vasoactive intestinal peptide(VIP)-like immunoreactivity in nerve cell bodies and axons of the myenteric plexus and circular muscle of the small intestine is consistent with VIP being the transmitter of enteric inhibitory neurons. Immunoreactivity for VIP was found in nerve cell bodies of the myenteric plexus and in axons within the myenteric plexus and circular muscle. When the axons in the myenteric plexus were interrupted, there was accumulation of material showing reactivity for VIP on the oral side, indicating that the neurons project in an anal direction. The VIP-like immunoreactivity in axons which supply the circular muscle disappeared after a myectomy in which the overlying myenteric plexus was removed, but remained intact when extrinsic nerves were served. The projections of VIP neurons from the myenteric plexus to the circular muscle correspond to the expected projections of enteric inhibitory neurons determined by functional studies.

Animals↗

PubMed1999

Two networks of electrically coupled inhibitory neurons in neocortex.

Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.

Action Potentials↗

PubMed1979

Does 5-hydroxytryptamine influence "purinergic" inhibitory neurons in the intestine?

Intrinsic inhibitory neurons to guinea pig taenia coli and small bowel circular muscle were activated by transmural electrical stimulation, and the postinhibitory contractile response of the muscle was utilized to evaluate whether or not the neuronal action of 5-hydroxytryptamine (5HT) was associated with the inhibitory neurons. The postinhibitory contractile responses of the small intestinal circular muscle were unaffected by 5HT. The 5HT antagonist methysergide also did not affect the poststimulus contractile response of the circular muscle. The amplitude and area under the contractile curve of the poststimulus contractile response of the taenia coli were reduced and the amplitude of the relaxation response to electrical stimulation was increased in one-half of the preparations after application of 5HT. Methysergide did not alter the poststimulus contractile response of the taenia coli. 5HT is implicated as a neurotransmitter substance for slow synaptic excitation within the enteric nervous system of the guinea pig small intestine; however, the 5HT synapses do not appear to be present on the "purinergic" inhibitory neurons nor on neurons that synaptically influence the inhibitory neurons.

Animals↗

PubMed1993

Metabotropic glutamate receptors mediate a post-tetanic excitation of guinea-pig hippocampal inhibitory neurones.

1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors. 2. Tetanic stimulation of afferent fibres caused an increase, of duration 0.5-2.5 min, in the frequency of spontaneous Cl(-)-mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials. 3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials. 4. Application of the metabotropic glutamate receptor agonist, trans-1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10 microM increased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP frequency did not continue to increase with concentrations of tACPD above 20 microM. 5. tACPD depolarized inhibitory cells and reduced after-hyperpolarizing potentials. High concentrations (50-100 microM) of tACPD excited inhibitory cells to potentials at which they no longer discharged fast action potentials. 6. Both tetanic stimulation and tACPD led to the appearance in pyramidal cell pairs of simultaneous IPSPs which were not previously observed, suggesting that the same group of inhibitory cells was excited in both cases. 7. Low concentrations of tACPD (3-10 microM) enhanced IPSP responses to tetanic stimuli, while the effects of tetanic stimuli were occluded in the presence of high concentrations (20-30 microM) of tACPD. 8. We suggest that activation of metabotropic glutamate receptors during tetanic stimulation leads to a post-tetanic excitation of inhibitory cells that mediate Cl(-)-dependent IPSPs.

2-Amino-5-phosphonovalerate↗

PubMed1989

Effects of (-)baclofen on inhibitory neurons in the guinea pig hippocampal slice.

Intracellular recordings were made from electrophysiologically identified inhibitory neurons in the dentate hilus. (-)Baclofen (0.1-0.5 mumol/l), applied by the bath, strongly hyperpolarized inhibitory neurons, reduced their input resistance and induced outward currents under voltage clamp at holding potentials of -60 mV in cells recorded with KCl-filled electrodes. Increasing the (-)baclofen concentration (up to 1 mumol/l) did not increase the amplitude of the outward current, but increased its duration. (-)Baclofen depressed Cl-dependent IPSPs evoked by perforant path stimulation in inhibitory neurons, granule cells and CA3 neurons. In the case of inhibitory neurons and CA3 neurons, depression of IPSPs, membrane hyperpolarization and increase in membrane conductance concurred. All effects were blocked by BaCl2 (1 mmol/l) in the superfusate. In the case of granule cells, depression of IPSPs by (-)baclofen outlasted an only small membrane hyperpolarization, conductance increase or outward current. High concentrations (up to 10 mumol/l) of (-)baclofen depressed evoked IPSPs of granule cells for an extended period of time, but the other effects remained small and transient. IPSPs elicited in granule cells by microdrop application of glutamate to the dentate hilus were also blocked by (-)baclofen, but spontaneous IPSPs were only reduced in amplitude. We suggest that the blockade of GABAA receptor-mediated IPSPs of hippocampal neurons by the GABAB receptor agonist (-)baclofen can be explained by a K-dependent hyperpolarization of inhibitory neurons.

Animals↗

PubMed1981

Release of 3H-gamma-aminobutyric acid (GABA) by inhibitory neurons of the crayfish.

Inhibitory neurons innervating the muscle receptor organ (MRO) of crayfish were used to study the uptake and release of tritiated GABA. MROs that have been directly exposed to 3H GABA for 60--75 min release radioactivity during low-frequency electrical stimulation. When ganglia containing the inhibitory cell bodies are exposed to 3H GABA, the isotope travels along a pathway unique to the inhibitory axon, at rates that range between 160 and 240 mm per day. Electrical stimulation of inhibitory axons whose cell bodies have been exposed to 3H GABA for 4--5 hr produces release of isotope from isolated MROs. Low calcium, high magnesium exposure prevents the stimulus-dependent release of radioactivity. Thin layer chromatographic analyses indicate that GABA comprises at least a major fraction of the radioactivity collected from stimulated preparations. A number of unidentified radioactive compounds are usually present with GABA, and it is suggested that most of these are catabolites of GABA.

Animals↗

PubMed2006

Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin.

Mammalian cortex contains a diversity of inhibitory neuron types, each with distinct morphological, immunochemical, and/or physiological properties. In rat cortex, chemical markers distinguish at least four distinct and nonoverlapping neuron classes based on expression of parvalbumin (PV), somatostatin (SST), calretinin (CR), and cholecystokinin (CCK). It has generally been assumed that these classifications should also apply to other rodent species. In mouse cortex, however, we found significant colocalization of SST and CR in inhibitory neurons; about 30% of SST-positive cells contained CR, and about 33% of CR-positive cells contained SST across frontal, somatosensory (S1), and visual cortex (V1). The SST and CR colocalized cells were concentrated in layer 2/3. We further characterized morphological and physiological properties of the mouse cortical inhibitory neuron types that express SST by using "GIN" transgenic mice, in which GFP is expressed in a subset of SST inhibitory neurons (see Oliva et al. [2000] J Neurosci 20:3354-3368). Generally, both SST/CR+ cells and SST/CR- cells exhibited morphological features of Martinotti cells as described in rat cortex, and they also had similar accommodating spike-firing patterns. However, they differed significantly in quantitative comparisons of morphology and spike shapes. SST/CR+ cells had more horizontally extended dendritic fields and more primary process than did SST/CR- cells; and SST/CR- cells had narrower action potential widths and faster afterhyperpolarization than did SST/CR+ cells. Thus, our data show an important species difference in the chemical distinction of inhibitory neuron subtypes, and indicate that colocalization of CR in SST cells correlates with different morphological and physiological features.

Action Potentials↗

PubMed1989

Effects of acute and chronic administration of Leu-enkephalin on cultured serotonergic neurons: evidence for opioids as inhibitory neuronal growth factors.

Leu-enkephalin, at concentrations between 18 microM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59%, P less than 0.05)- and 5 (38%, P less than 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191%, P less than 0.05)- and 5 (140%, P less than 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.

Aminopeptidases↗

PubMed2006

Expression pattern of voltage-dependent calcium channel subunits in hippocampal inhibitory neurons in mice.

Different subtypes of voltage-dependent calcium channels (VDCCs) generate various types of calcium currents that play important role in neurotransmitter release, membrane excitability, calcium transients and gene expression. Well-established differences in the physiological properties and variable sensitivity of hippocampal GABAergic inhibitory neurons to excitotoxic insults suggest that the calcium homeostasis, thus VDCC subunits expression pattern is likely different in subclasses of inhibitory cells. Using double-immunohistochemistry, here we report that in mice: 1) Cav2.1 and Cav3.1 subunits are expressed in almost all inhibitory neurons; 2) subunits responsible for the L-type calcium current (Cav1.2 and Cav1.3) are infrequently co-localized with calretinin inhibitory cell marker while Cav1.3 subunit, at least in part, tends to compensate for the low expression of Cav1.2 subunit in parvalbumin-, metabotropic glutamate receptor 1alpha- and somatostatin-immunopositive inhibitory neurons; 3) Cav2.2 subunit is expressed in the majority of inhibitory neurons except in calbindin-reactive inhibitory cells; 4) Cav2.3 subunit is expressed in the vast majority of the inhibitory cells except in parvalbumin- and calretinin-immunoreactive neurons where the proportion of expression of this subunit is considerably lower. These data indicate that VDCC subunits are differentially expressed in hippocampal GABAergic interneurons, which could explain the diversity in their electrophysiological properties, the existence of synaptic plasticity in certain inhibitory neurons and their vulnerability to stressful stimuli.

Animals↗

PubMed1993

Heterogeneity in presynaptic regulation of GABA release from hippocampal inhibitory neurons.

Release of GABA from the terminals of hippocampal inhibitory neurons is inhibited by activation of GABAB autoreceptors and mu opioid receptors. However, it is not known whether these presynaptic processes affect all inhibitory synapses equally. We examined the effects of the GABAB receptor agonist baclofen and the mu opioid receptor agonist DAGO on postsynaptic currents evoked by minimal stimulation of inhibitory fibers (meIPSCs) in area CA3. Baclofen reversibly depressed approximately half of the meIPSCs evoked in the stratum pyramidale. The remaining meIPSCs were unaffected despite a coincident depression of spontaneous IPSCs. In contrast, all meIPSCs were depressed by DAGO. In addition, minimal stimulation in the stratum radiatum evoked meIPSCs that were always depressed by baclofen. These results indicate that regulation of GABA release by GABAB autoreceptors occurs at a subset of inhibitory synapses and that GABAB-resistant inhibitory synapses are located on pyramidal neuron somata. Hippocampal inhibitory neurons may be heterogeneous with respect to presynaptic receptor-mediated regulation of GABA release.

Analgesics↗

PubMed2002

Spinal inhibitory neurons that modulate cutaneous sensory pathways during locomotion in a simple vertebrate.

During locomotion, reflex responses to sensory stimulation are usually modulated and may even be reversed. This is thought to be the result of phased inhibition, but the neurons responsible are usually not known. When the hatchling Xenopus tadpole swims, responses to cutaneous stimulation are modulated. This occurs because sensory pathway interneurons receive rhythmic glycinergic inhibition broadly in phase with the motor discharge on the same side of the trunk. We now describe a new whole-cell recording preparation of the Xenopus tadpole CNS. This has been used with neurobiotin injection to define the passive and firing properties of spinal ascending interneurons and their detailed anatomy. Paired recordings show that they make direct, glycinergic synapses onto spinal sensory pathway interneurons, and the site of contact can be seen anatomically. During swimming, ascending interneurons fire rhythmically. Analysis shows that their firing is more variable and not as reliable as other interneurons, but the temporal pattern of their impulse activity is suitable to produce the main peak of gating inhibition in sensory pathway interneurons. Ascending interneurons are not excited at short latency after skin stimulation but are strongly active after repetitive skin stimulation, which evokes vigorous and slower struggling movements. We conclude that ascending interneurons are a major class of modulatory neurons producing inhibitory gating of cutaneous sensory pathways during swimming and struggling.

Afferent Pathways↗

PubMed2004

Presumed inhibitory neurons in the macaque inferior temporal cortex: visual response properties and functional interactions with adjacent neurons.

Neurons in area TE of the monkey inferior temporal cortex respond selectively to images of particular objects or their characteristic visual features. The mechanism of generation of the stimulus selectivity, however, is largely unknown. This study addresses the role of inhibitory TE neurons in this process by examining their visual response properties and interactions with adjacent target neurons. We applied cross-correlation analysis to spike trains simultaneously recorded from pairs of adjacent neurons in anesthetized macaques. Neurons whose activity preceded a decrease in activity from their partner were presumed to be inhibitory neurons. Excitatory neurons were also identified as the source neuron of excitatory linkage as evidenced by a sharp peak displaced from the 0-ms bin in cross-correlograms. Most inhibitory neurons responded to a variety of visual stimuli in our stimulus set, which consisted of several dozen geometrical figures and photographs of objects, with a clear stimulus preference. On average, 10% of the stimuli increased firing rates of the inhibitory neurons. Both excitatory and inhibitory neurons exhibited a similar degree of stimulus selectivity. Although inhibitory neurons occasionally shared the most preferred stimuli with their target neurons, overall stimulus preferences were less similar between adjacent neurons with inhibitory linkages than adjacent neurons with common inputs and/or excitatory linkages. These results suggest that inhibitory neurons in area TE are activated selectively and exert stimulus-specific inhibition on adjacent neurons, contributing to shaping of stimulus selectivity of TE neurons.

Action Potentials↗

PubMed2001

Direction selectivity of excitatory and inhibitory neurons in ferret visual cortex.

Direction selectivity is a characteristic feature of neurons in the visual cortex of higher mammals. Excitatory and inhibitory cortical neurons receive different patterns of synaptic connections resulting in different receptive field properties. We have analyzed the direction tuning of excitatory and inhibitory neurons of ferret visual cortex using single unit recordings. Direction tuning was constant among neurons in a vertical column. The majority (> 80%) of excitatory (regular spiking) neurons were direction tuned or direction biased. Fast spiking (inhibitory) neurons were orientation, but only weakly or not direction tuned. This indicates that excitatory and inhibitory neurons have different functions in visual processing and their different integration in thalamocortical and intracortical circuits results in a diversification of receptive field properties.

Action Potentials↗

PubMed2003

Inhibitory neurons from fetal rat cerebral cortex exert delayed axon formation and active migration in vitro.

Inhibitory and excitatory neurons exhibit distinct patterns of development in the mammalian cerebral cortex. The morphological development of inhibitory and excitatory neurons derived from fetal rat cerebral cortex has now been compared in vitro. Inhibitory neurons were identified by immunofluorescence staining with antibodies to gamma-aminobutyric acid, and axon formation was detected by staining with antibodies to phosphorylated neurofilaments. In chemically defined, glia-free and low-density cultures, excitatory neurons formed axons within three days of plating. By contrast, inhibitory neurons required more than six days to form axons. Time-lapse analysis over six days revealed that most inhibitory neurons were bipolar and that their two processes exhibited alternate growth and retraction without giving rise to axons. Movement of the cell body towards the growing process was apparent in about one-half of inhibitory neurons, whereas such movement was never seen in excitatory neurons. The migratory behavior of neurons was further investigated by culture on a glial cell monolayer. Inhibitory neurons migrated over substantially larger distances than did excitatory neurons. The centrosome of inhibitory neurons translocated to the base of the newly emerging leading process, suggesting the existence of a force that pulls intracellular organelles towards the leading process. Centrosome translocation was not detected in excitatory neurons. These observations suggest that the developmental programs of excitatory and inhibitory neurons differ. Inhibitory neurons thus possess a more effective cytoskeletal machinery for migration than excitatory neurons and they form axons later.

Animals↗

PubMed1996

Inhibitory neurons in the human epileptogenic temporal neocortex. An immunocytochemical study.

Immunocytochemical methods were used to study alterations in inhibitory neuronal circuits in human neocortex resected during surgical treatment of intractable temporal epilepsy associated or not with brain tumours. The epileptogenic cortex was characterized and divided into spiking or non-spiking zones by intraoperative electrocorticography (ECOG). The resected cortex was cut into blocks, sectioned and stained immunocytochemically for visualization of glutamic acid decarboxylase (GAD), the calcium-binding protein, parvalbumin (PV) and glial fibrillary acidic protein (GFAP). A variety of alterations in cortical neuronal circuits as revealed by immunocytochemical and histological methods were found. Similar alterations in inhibitory neuronal circuits appear to occur independently of the primary epileptogenic site and pathology associated with epilepsy, which suggests that there is possibly a common basic underlying mechanism that leads to seizure activity. These changes were apparently unrelated to ECOG findings at surgery, which bring into question the value of the use of interictal epileptic discharges recorded by ECOG to guide cortical resections. The most conspicuous and common change was the loss of chandelier cells. The finding that these cells are among the most vulnerable types of GABAergic interneurons in the epileptogenic temporal cortex indicates that they might be of great functional importance, since the axon terminals of chandelier cells are likely to exert powerful regulation of impulse generation in cortical pyramidal cells. Therefore, these cells might represent a key component in the aetiology of human epilepsy.

Adolescent↗

PubMed2004

Targeted gene delivery to telencephalic inhibitory neurons by directional in utero electroporation.

Telencephalic inhibitory neurons originate in the ganglionic eminences and migrate to the cerebral cortex following a tangential trajectory, before they differentiate and integrate within the local circuitry. Current studies of interneuron development and function benefit from the use of knock-out and transgenic mice, whereas none take advantage of the versatility of in utero electroporation. Here, we show how in utero electroporation can be directed to the ganglionic eminences to specifically target gene expression to interneurons. Electroporation of GFP-encoding plasmids into the ganglionic eminences results in selective labeling of migrating interneurons during development. In the adult brain of electroporated animals, a wide variety of cortical, hippocampal and olfactory bulb interneurons are labeled. We also show that GFP-expressing interneurons can be visualized in living slices of adult cerebral cortex, where they display normal electrophysiological properties. Photostimulation studies using acute slices show that cortical GFP+ interneurons receive normal, layer-specific synaptic input, indicating that these neurons integrate within the local cortical circuitry. Ganglionic eminence-directed in utero electroporation is therefore an effective, rapid, and versatile method of selectively transfecting telencephalic interneurons, optimal for both developmental studies and adult functional studies.

Animals↗

PubMed1999

Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus.

Synaptic NMDA-type glutamate receptors are anchored to the second of three PDZ (PSD-95/Discs large/ZO-1) domains in the postsynaptic density (PSD) protein PSD-95. Here, we report that citron, a protein target for the activated form of the small GTP-binding protein Rho, preferentially binds the third PDZ domain of PSD-95. In GABAergic neurons from the hippocampus, citron forms a complex with PSD-95 and is concentrated at the postsynaptic side of glutamatergic synapses. Citron is expressed only at low levels in glutamatergic neurons in the hippocampus and is not detectable at synapses onto these neurons. In contrast to citron, p135 SynGAP, an abundant synaptic Ras GTPase-activating protein that can bind to all three PDZ domains of PSD-95, and Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) are concentrated postsynaptically at glutamatergic synapses on glutamatergic neurons. CaM kinase II is not expressed and p135 SynGAP is expressed in less than half of hippocampal GABAergic neurons. Segregation of citron into inhibitory neurons does not occur in other brain regions. For example, citron is expressed at high levels in most thalamic neurons, which are primarily glutamatergic and contain CaM kinase II. In several other brain regions, citron is present in a subset of neurons that can be either GABAergic or glutamatergic and can sometimes express CaM kinase II. Thus, in the hippocampus, signal transduction complexes associated with postsynaptic NMDA receptors are different in glutamatergic and GABAergic neurons and are specialized in a way that is specific to the hippocampus.

Amino Acid Sequence↗