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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chief inhibitory neurons of the mammalian brain, GABAergic neurons, are comprised of a myriad of diverse neuronal subtypes. To facilitate the study of these neurons, transgenic mice were generated that express enhanced green fluorescent protein (EGFP) in subpopulations of GABAergic neurons. In one of the resulting transgenic lines, called GIN (GFP-expressing Inhibitory Neurons), EGFP was found to be expressed in a subpopulation of somatostatin-containing GABAergic interneurons in the hippocampus and neocortex. In both live and fixed brain preparations from these mice, detailed microanatomical features of EGFP-expressing interneurons were readily observed. In stratum oriens of the hippocampus, EGFP-expressing interneurons were comprised almost exclusively of oriens/alveus interneurons with lacunosum-moleculare axon arborization (O-LM cells). In the neocortex, the somata of EGFP-expressing interneurons were largely restricted to layers II-IV and upper layer V. In hippocampal area CA1, two previously uncharacterized subtypes of interneurons were identified using the GIN mice: stratum pyramidale interneurons with lacunosum-moleculare axon arborization (P-LM cells) and stratum radiatum interneurons with lacunosum-moleculare axon arborization (R-LM cells). These newly identified interneuronal subtypes appeared to be closely related to O-LM cell, as they selectively innervate stratum lacunosum-moleculare. Whole-cell patch-clamp recordings revealed that these cells were fast-spiking and showed virtually no spike frequency accommodation. The microanatomical features of these cells suggest that they function primarily as "input-biasing" neurons, in that synaptic volleys in stratum radiatum would lead to their activation, which in turn would result in selective suppression of excitatory input from the entorhinal cortex onto CA1 pyramidal cells.
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PMID:Novel hippocampal interneuronal subtypes identified using transgenic mice that express green fluorescent protein in GABAergic interneurons. 1077 98

Excitotoxicity, resulting from the excessive release of glutamate, is thought to contribute to a variety of neurological disorders, including epilepsy. Excitotoxic damage to dendrites, i.e., dendrotoxicity, is often characterized by the formation of large dendritic swellings, or "beads." Here, we show that hippocampal interneurons that express the neuropeptide somatostatin are highly vulnerable to the excitotoxic effects of the ionotropic glutamate receptor agonist kainate. Brief, focal iontophoretic application of kainate rapidly induced bead formation in dendrites of somatostatinergic interneurons that express green fluorescent protein (GFP) from mice of the transgenic line GIN (GFP-expressing inhibitory neurons). Surprisingly, beads often did not form at the site of kainate application or even in the dendritic segment to which kainate was applied; instead, dendritic beading occurred more distally, often encompassing all branches distal to the application site. We have termed this phenomena, "distally directed dendrotoxicity." Distally directed beading was induced regardless of the branch order of the site of application and was found to be dependent on activation of voltage-gated sodium channels. Subsequent to induction, distally directed beading would reverse in most cells; in other cells, however, beading irreversibly invaded proximal dendritic segments and gradually encompassed the entire dendritic tree. These results demonstrate that distal dendritic segments are highly vulnerable to excitotoxic injury and imply that excessive excitatory activity originating in one synaptic pathway can impact synapses at more distal dendritic segments of the same neuron. The discovery of this phenomenon will likely be important in understanding interneuronal dysfunction following excitotoxic injury.
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PMID:Distally directed dendrotoxicity induced by kainic Acid in hippocampal interneurons of green fluorescent protein-expressing transgenic mice. 1222 59

GABA-releasing inhibitory interneurons in the cerebral cortex can be classified by their neurochemical content, firing patterns, or axonal targets, to name the most common criteria, but whether classifications using different criteria converge on the same neuronal subtypes, and how many such subtypes exist, is a matter of much current interest and considerable debate. To address these issues, we generated transgenic mice expressing green fluorescent protein (GFP) under control of the GAD67 promoter. In two of these lines, named X94 and X98, GFP expression in the barrel cortex was restricted to subsets of somatostatin-containing (SOM+) GABAergic interneurons, similar to the previously reported "GIN" line (Oliva et al., 2000), but the laminar distributions of GFP-expressing (GFP+) cell bodies in the X94, X98, and GIN lines were distinct and nearly complementary. We compared neurochemical content and axonal distribution patterns of GFP+ neurons among the three lines and analyzed in detail electrophysiological properties in a dataset of 150 neurons recorded in whole-cell, current-clamp mode. By all criteria, there was nearly perfect segregation of X94 and X98 GFP+ neurons, whereas GIN GFP+ neurons exhibited intermediate properties. In the X98 line, GFP expression was found in infragranular, calbindin-containing, layer 1-targeting ("Martinotti") cells that had a propensity to fire low-threshold calcium spikes, whereas X94 GFP+ cells were stuttering interneurons with quasi fast-spiking properties, residing in and targeting the thalamo-recipient neocortical layers. We conclude that much of the variability previously attributed to neocortical SOM+ interneurons can be accounted for by their natural grouping into distinct subtypes.
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PMID:Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. 1685 31

Classification of inhibitory interneurons is critical in determining their role in normal information processing and pathophysiological conditions such as epilepsy. Classification schemes have relied on morphological, physiological, biochemical, and molecular criteria; and clear correlations have been demonstrated between firing patterns and cellular markers such as neuropeptides and calcium-binding proteins. This molecular diversity has allowed generation of transgenic mouse strains in which GFP expression is linked to the expression of one of these markers and presumably a single subtype of neuron. In the GIN mouse (EGFP-expressing Inhibitory Neurons), a subpopulation of somatostatin-containing interneurons in the hippocampus and neocortex is labeled with enhanced green fluorescent protein (EGFP). To optimize the use of the GIN mouse, it is critical to know whether the population of somatostatin-EGFP-expressing interneurons is homogeneous. We performed unsupervised cluster analysis on 46 EGFP-expressing interneurons, based on data obtained from whole cell patch-clamp recordings. Cells were classified according to a number of electrophysiological variables related to spontaneous excitatory postsynaptic currents (sEPSCs), firing behavior, and intrinsic membrane properties. EGFP-expressing interneurons were heterogeneous and at least four subgroups could be distinguished. In addition, multiple discriminant analysis was applied to data collected during whole cell recordings to develop an algorithm for predicting the group membership of newly encountered EGFP-expressing interneurons. Our data are consistent with a heterogeneous population of neurons based on electrophysiological properties and indicate that EGFP expression in the GIN mouse is not restricted to a single class of somatostatin-positive interneuron.
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PMID:Electrophysiological classification of somatostatin-positive interneurons in mouse sensorimotor cortex. 1670 15

Target cell-specific differences in short-term plasticity have been attributed to differences in the initial release probability of synapses. Using GIN (GFP-expressing inhibitory neurons) transgenic mice that express enhanced green fluorescent protein (EGFP) in a subset of interneurons containing somatostatin, we show that Schaffer collateral synapses onto the EGFP-expressing somatostatin interneurons in CA1 have very large short-term facilitation, even larger facilitation than onto pyramidal cells, in contrast to the majority of interneurons that have little or no facilitation. Using a combination of electrophysiological recordings and mathematical modeling, we show that the large short-term facilitation is caused both by a very low initial release probability and by synaptic activation of presynaptic kainate receptors that increase release probability on subsequent stimuli. Thus, we have discovered a novel mechanism for target cell-specific short-term plasticity at Schaffer collateral synapses in which the activation of presynaptic kainate receptors by synaptically released glutamate contributes to large short-term facilitation, enabling selective enhancement of the inputs to a subset of interneurons.
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PMID:Presynaptic kainate receptor activation is a novel mechanism for target cell-specific short-term facilitation at Schaffer collateral synapses. 1705 Jul 18

GABAergic interneurons constitute a heterogeneous group of cells that exert a powerful control on network excitability and are responsible for the oscillatory behavior crucial for information processing in the brain. These cells have been differently classified according to their morphological, neurochemical, and physiological characteristics. Here, whole cell patch clamp recordings were used to further characterize, in transgenic mice expressing EGFP in a subpopulation of GABAergic interneurons containing somatostatin (GIN mice), the functional properties of EGFP-positive cells in stratum oriens of the CA1 region of the hippocampus, in slice cultures obtained from P8 old animals. These cells showed passive and active membrane properties similar to those found in stratum oriens interneurons projecting to stratum lacunosum-moleculare. Moreover, they exhibited different firing patterns that were maintained upon membrane depolarization: irregular (48%), regular (30%), and clustered (22%). Trains of action potentials in interneurons evoked in a minority of principal cells (3/45) small amplitude GABAergic currents that at 20 Hz underwent short-term depression. In contrast, excitatory connections between principal cells and EGFP-positive interneurons were highly reliable (17/55) and exhibited a frequency and use-dependent facilitation particularly in the gamma band. In addition, recordings from paired of interconnected EGFP-positive cells revealed in 47% of the cases electrical coupling, which was abolished by carbenoxolone (200 microM). On average, the coupling coefficient was 0.21 +/- 0.07. When electrical coupling was particularly strong it acted as a powerful low-pass filter, thus contributing to alter the output of individual cells. In conclusion, it appears that the dynamic interaction between cells with various firing patterns could differently affect GABAergic signaling, leading, as suggested by simulation data, to a wide range of interneuronal communication within the hippocampal network.
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PMID:Signaling properties of stratum oriens interneurons in the hippocampus of transgenic mice expressing EGFP in a subset of somatostatin-containing cells. 1745 32

The specific functions of subtypes of cortical inhibitory neurons are not well understood. This is due in part to a dearth of information about the behaviors of interneurons under conditions when the surrounding circuit is in an active state. We investigated the firing behavior of a subset of inhibitory interneurons, identified using mice that express green fluorescent protein (GFP) in a subset of somatostatin-expressing inhibitory cells ("GFP-expressing inhibitory neuron" [GIN] cells). The somata of the GIN cells were in layer 2/3 of somatosensory cortex and had dense, layer 1-projecting axons that are characteristic of Martinotti neurons. Interestingly, GIN cells fired similarly during a variety of diverse activating conditions: when bathed in fluids with low-divalent cation concentrations, when stimulated with brief trains of local synaptic inputs, when exposed to group I metabotropic glutamate receptor agonists, or when exposed to muscarinic cholinergic receptor agonists. During these manipulations, GIN cells fired rhythmically and persistently in the theta-frequency range (3-10 Hz). Synchronous firing was often observed and its strength was directly proportional to the magnitude of electrical coupling between GIN cells. These effects were cell type specific: the four manipulations that persistently activated GIN cells rarely caused spiking of regular-spiking (RS) pyramidal cells or fast-spiking (FS) inhibitory interneurons. Our results suggest that supragranular GIN interneurons form an electrically coupled network that exerts a coherent 3- to 10-Hz inhibitory influence on its targets. Because GIN cells are more readily activated than RS and FS cells, it is possible that they act as "first responders" when cortical excitatory activity increases.
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PMID:Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex. 1879 98

A large variety of distinct locally connected GABAergic cells are present in the hippocampus. By releasing GABA into principal cells and interneurons, they exert a powerful control on neuronal excitability and are responsible for network oscillations crucial for information processing in the brain. Here, whole-cell patch clamp recordings in current and voltage clamp mode were used to study the functional role of nicotinic acetylcholine receptors (nAChRs) on the firing properties of stratum oriens interneurons in hippocampal slices from transgenic mice expressing enhanced green fluorescent protein in a subpopulation of GABAergic cells containing somatostatin (GIN mice). Unexpectedly, activation of nAChRs by nicotine or endogenously released acetylcholine strongly enhanced spike frequency adaptation. This effect was blocked by apamin, suggesting the involvement of small calcium-dependent potassium channels (SK channels). Nicotine-induced reduction in firing frequency was dependent on intracellular calcium rise through calcium-permeable nAChRs and voltage-dependent calcium channels activated by the depolarizing action of nicotine. Calcium imaging experiments directly showed that nicotine effects on firing rate were correlated with large increases in intracellular calcium. Furthermore, blocking ryanodine receptors with ryanodine or sarcoplasmic-endoplasmic reticulum calcium ATPase with thapsygargin or cyclopiazonic acid fully prevented the effects of nicotine, suggesting that mobilization of calcium from the internal stores contributed to the observed effects. By regulating cell firing, cholinergic signalling through nAChRs would be instrumental for fine-tuning the output of stratum oriens interneurons and correlated activity at the network level.
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PMID:Activation of nicotinic acetylcholine receptors enhances a slow calcium-dependent potassium conductance and reduces the firing of stratum oriens interneurons. 1973 87

In temporal lobe epilepsy, seizures initiate in or near the hippocampus, which frequently displays loss of neurons, including inhibitory interneurons. It is unclear whether surviving interneurons function normally, are impaired, or develop compensatory mechanisms. We evaluated GABAergic interneurons in the hilus of the dentate gyrus of epileptic pilocarpine-treated GIN mice, specifically a subpopulation of somatostatin interneurons that expresses enhanced green fluorescence protein (GFP). GFP-immunocytochemistry and stereological analyses revealed substantial loss of GFP-positive hilar neurons (GPHNs) but increased GFP-positive axon length per dentate gyrus in epileptic mice. Individual biocytin-labeled GPHNs in hippocampal slices from epileptic mice also had larger somata, more axon in the molecular layer, and longer dendrites than controls. Dual whole-cell patch recording was used to test for monosynaptic connections from hilar GPHNs to granule cells. Unitary IPSCs (uIPSCs) recorded in control and epileptic mice had similar average rise times, amplitudes, charge transfers, and decay times. However, the probability of finding monosynaptically connected pairs and evoking uIPSCs was 2.6 times higher in epileptic mice compared to controls. Together, these findings suggest that surviving hilar somatostatin interneurons enlarge, extend dendrites, sprout axon collaterals in the molecular layer, and form new synapses with granule cells. These epilepsy-related changes in cellular morphology and connectivity may be mechanisms for surviving hilar interneurons to inhibit more granule cells and compensate for the loss of vulnerable interneurons.
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PMID:Surviving hilar somatostatin interneurons enlarge, sprout axons, and form new synapses with granule cells in a mouse model of temporal lobe epilepsy. 1990 72

The neocortex contains multiple types of inhibitory neurons whose properties suggest they may play different roles within the cortical circuit. By recording from three cell types during two distinct network states (UP and DOWN states) in vitro, we were able to quantify differences in firing characteristics between these cells during different network regimes. We recorded from regular-spiking (RS) excitatory cells and two types of inhibitory neurons, the fast-spiking (FS) neurons and GFP- (and somatostatin-) expressing inhibitory neurons (GIN), in layer 2/3 of slices from mouse somatosensory neocortex. Comparisons of firing characteristics between these cells during UP- and DOWN-states showed several patterns. First, of these cell types, only GIN cells fired persistently during DOWN-states, whereas all three cell types fired readily during UP-states. Second, the onset of firing and distribution of action potentials throughout UP-states differed by cell type, showing that FS cell UP-state firing occurred preferentially near the beginning of the UP-state, whereas the firing of RS cells was slower to develop at the start of the UP-state, and GIN cell firing was sustained throughout the duration of the UP-state. Finally, membrane potential and spike correlations between heterogeneous cell types were more pronounced during UP-states and, in the case of RS synapses onto GIN cells, varied throughout the UP-state. These results suggest that there is a division of labor between FS and GIN cells as the UP-state progresses and suggest that GIN cells could be important in the termination of UP-states.
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PMID:The roles of somatostatin-expressing (GIN) and fast-spiking inhibitory interneurons in UP-DOWN states of mouse neocortex. 2053 67


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