Page 1. Ideggyogy Sz 2007;60(3–4):187–191. 187 ELÔZETES KÖZLEMÉNY MOLECULAR ARCHITECTURE OF THE C... more Page 1. Ideggyogy Sz 2007;60(3–4):187–191. 187 ELÔZETES KÖZLEMÉNY MOLECULAR ARCHITECTURE OF THE CANNABINOID SIGNALING SYSTEM IN THE CORE OF THE NUCLEUS ACCUMBENS Ferenc Mátyás1 ...
The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when asso... more The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.
Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, ... more Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction-related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb)--which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachi-donoyl-glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-alpha), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-alpha and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-alpha distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals...
Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in... more Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in the thalamus; however, what determines their duration is presently unclear. Here, we measured somatic activity of excitatory thalamocortical (TC) cells together with axonal activity of reciprocally coupled inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle alterations in their firing in vivo. We found that spindles with different durations were paralleled by distinct nRT activity, and nRT firing sharply dropped before the termination of all spindles. Both initial nRT and TC activity was correlated with spindle length, but nRT correlation was more robust. Analysis of spindles evoked by optogenetic activation of nRT showed that spindle probability, but not spindle length, was determined by the strength of the light stimulus. Our data indicate that during natural sleep a dynamically fluctuating thalamocortical network controls the duration of sleep spindles via the ma...
Transgenic mice are overtaking the role of model animals in neuroscience. They are used in develo... more Transgenic mice are overtaking the role of model animals in neuroscience. They are used in developmental, anatomical, and physiological as well as experimental neurology. However, most results on the organization of the nervous system derive from the rat. The rat hippocampus and its neuronal elements have been thoroughly investigated, revealing remarkable functional and morphological diversity and specificity among hippocampal interneurons. Our aim was to examine the properties of distinct hippocampal interneuron populations, i.e., those immunoreactive for calcium-binding proteins (parvalbumin, calbindin, and calretinin), neuropeptides (cholecystokinin, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide), and certain receptors (metabotropic glutamate receptor 1alpha, cannabinoid receptor type 1) in four strains of mice widely used in transgenic technology, and to compare their properties to those in the rat. Our data indicate that the distribution as well as the dendritic and axonal arborization of mouse interneurons immunoreactive for the different markers was identical in the examined mouse strains, and in most respects are similar to the features found in the rat. The postsynaptic targets of neurons terminating in the perisomatic (parvalbumin), proximal (calbindin), and distal (somatostatin) dendritic region, as well as on other interneurons (calretinin), also matched those found in the rat. However, a few significant differences could also be observed between the two species in addition to the already described immunoreactivity of mossy cells for calretinin: the absence of spiny calretinin-immunoreactive interneurons in the CA3 region, sparse contacts between calretinin-immunoreactive interneurons, and the axon staining for somatostatin and neuropil labeling for cholecystokinin. We can conclude that the morphofunctional classification of interneurons established in the rat is largely valid for mouse strains used in transgenic procedures.
Page 1. Ideggyogy Sz 2007;60(3–4):187–191. 187 ELÔZETES KÖZLEMÉNY MOLECULAR ARCHITECTURE OF THE C... more Page 1. Ideggyogy Sz 2007;60(3–4):187–191. 187 ELÔZETES KÖZLEMÉNY MOLECULAR ARCHITECTURE OF THE CANNABINOID SIGNALING SYSTEM IN THE CORE OF THE NUCLEUS ACCUMBENS Ferenc Mátyás1 ...
The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when asso... more The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.
Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, ... more Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction-related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb)--which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachi-donoyl-glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-alpha), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-alpha and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-alpha distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals...
Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in... more Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in the thalamus; however, what determines their duration is presently unclear. Here, we measured somatic activity of excitatory thalamocortical (TC) cells together with axonal activity of reciprocally coupled inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle alterations in their firing in vivo. We found that spindles with different durations were paralleled by distinct nRT activity, and nRT firing sharply dropped before the termination of all spindles. Both initial nRT and TC activity was correlated with spindle length, but nRT correlation was more robust. Analysis of spindles evoked by optogenetic activation of nRT showed that spindle probability, but not spindle length, was determined by the strength of the light stimulus. Our data indicate that during natural sleep a dynamically fluctuating thalamocortical network controls the duration of sleep spindles via the ma...
Transgenic mice are overtaking the role of model animals in neuroscience. They are used in develo... more Transgenic mice are overtaking the role of model animals in neuroscience. They are used in developmental, anatomical, and physiological as well as experimental neurology. However, most results on the organization of the nervous system derive from the rat. The rat hippocampus and its neuronal elements have been thoroughly investigated, revealing remarkable functional and morphological diversity and specificity among hippocampal interneurons. Our aim was to examine the properties of distinct hippocampal interneuron populations, i.e., those immunoreactive for calcium-binding proteins (parvalbumin, calbindin, and calretinin), neuropeptides (cholecystokinin, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide), and certain receptors (metabotropic glutamate receptor 1alpha, cannabinoid receptor type 1) in four strains of mice widely used in transgenic technology, and to compare their properties to those in the rat. Our data indicate that the distribution as well as the dendritic and axonal arborization of mouse interneurons immunoreactive for the different markers was identical in the examined mouse strains, and in most respects are similar to the features found in the rat. The postsynaptic targets of neurons terminating in the perisomatic (parvalbumin), proximal (calbindin), and distal (somatostatin) dendritic region, as well as on other interneurons (calretinin), also matched those found in the rat. However, a few significant differences could also be observed between the two species in addition to the already described immunoreactivity of mossy cells for calretinin: the absence of spiny calretinin-immunoreactive interneurons in the CA3 region, sparse contacts between calretinin-immunoreactive interneurons, and the axon staining for somatostatin and neuropil labeling for cholecystokinin. We can conclude that the morphofunctional classification of interneurons established in the rat is largely valid for mouse strains used in transgenic procedures.
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