Ionic mechanisms involved in arginine vasopressin-mediated excitation of auditory cortical and thalamic neurons.

The axons containing arginine vasopressin (AVP) from the hypothalamus innervate a variety of structures including the cerebral cortex, thalamus, hippocampus and amygdala. A plethora amount of evidence indicates that activation of the V subtype of the vasopressin receptors facilitates anxiety-like and fear responses. As an essential structure involved in fear and anxiety responses, the amygdala, especially the lateral nucleus of amygdala (LA), receives glutamatergic innervations from the auditory cortex and auditory thalamus where high density of V receptors have been detected.

Leptin excites basolateral amygdala principal neurons and reduces food intake by LepRb-JAK2-PI3K-dependent depression of GIRK channels.

Leptin is an adipocyte-derived hormone that modulates food intake, energy balance, neuroendocrine status, thermogenesis, and cognition. Whereas a high density of leptin receptors has been detected in the basolateral amygdala (BLA) neurons, the physiological functions of leptin in the BLA have not been determined yet. We found that application of leptin excited BLA principal neurons by activation of the long form leptin receptor, LepRb.

Neuromedin B excites central lateral amygdala neurons and reduces cardiovascular output and fear-potentiated startle.

Neuromedin B (NMB) and gastrin-releasing peptide (GRP) are the two mammalian analogs in the bombesin peptide family that exert a variety of actions including emotional processing, appetitive behaviors, cognition, and tumor growth. The bombesin-like peptides interact with three receptors: the NMB-preferring bombesin 1 (BB1) receptors, the GRP-preferring bombesin 2 (BB2) receptors and the orphan bombesin 3 (BB3) receptors. Whereas, injection of bombesin into the central amygdala reduces satiety and modulates blood pressure, the underlying cellular and molecular mechanisms have not been determined.

Ionic signalling mechanisms involved in neurokinin-3 receptor-mediated augmentation of fear-potentiated startle response in the basolateral amygdala.

The tachykinin peptides include substance P (SP), neurokinin A and neurokinin B, which interact with three G-protein-coupled neurokinin receptors, NK1Rs, NK2Rs and NK3Rs, respectively. Whereas high densities of NK3Rs have been detected in the basolateral amygdala (BLA), the functions of NK3Rs in this brain region have not been determined. We found that activation of NK3Rs by application of the selective agonist, senktide, persistently excited BLA principal neurons.

PLCβ-Mediated Depletion of PIP and ATP-Sensitive K Channels Are Involved in Arginine Vasopressin-Induced Facilitation of Neuronal Excitability and LTP in the Dentate Gyrus.

Arginine vasopressin (AVP) serves as a neuromodulator in the brain. The hippocampus is one of the major targets for AVP, as it has been demonstrated that the hippocampus receives vasopressinergic innervation and expresses AVP receptors. The dentate gyrus (DG) granule cells (GCs) serve as a gate governing the inflow of information to the hippocampus.

Roles of PLCβ, PIP , and GIRK channels in arginine vasopressin-elicited excitation of CA1 pyramidal neurons.

Arginine vasopressin (AVP) is a hormone exerting vasoconstrictive and antidiuretic action in the periphery and serves as a neuromodulator in the brain. Although the hippocampus receives vasopressinergic innervation and AVP has been shown to facilitate the excitability of CA1 pyramidal neurons, the involved ionic and signaling mechanisms have not been determined. Here we found that AVP excited CA1 pyramidal neurons by activation of V receptors.

Ionic and signaling mechanisms involved in neurotensin-mediated excitation of central amygdala neurons.

Neurotensin (NT) serves as a neuromodulator in the brain where it regulates a variety of physiological functions. Whereas the central amygdala (CeA) expresses NT peptide and NTS1 receptors and application of NT has been shown to excite CeA neurons, the underlying cellular and molecular mechanisms have not been determined. We found that activation of NTS1 receptors increased the neuronal excitability of the lateral nucleus (CeL) of CeA.

Activation of V vasopressin receptors excite subicular pyramidal neurons by activating TRPV1 and depressing GIRK channels.

Arginine vasopressin (AVP) is a nonapeptide that serves as a neuromodulator in the brain and a hormone in the periphery that regulates water homeostasis and vasoconstriction. The subiculum is the major output region of the hippocampus and an integral component in the networks that processes sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whereas the subiculum expresses high densities of AVP-binding sites and AVP has been shown to increase the synaptic excitability of subicular pyramidal neurons, the underlying cellular and molecular mechanisms have not been determined.

Involvement of TRPC5 channels, inwardly rectifying K channels, PLCβ and PIP in vasopressin-mediated excitation of medial central amygdala neurons.

Activation of V vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K (Kir) channel The cationic conductance activated by V receptors is identified as TRPC5 channels PLCβ-mediated depletion of PIP is involved in V receptor-elicited excitation of CeM neurons Intracellular Ca release and PKC are unnecessary for V receptor-mediated excitation of CeM neurons ABSTRACT: Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviours, pain and alcohol use disorders. Whereas activation of V receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signalling mechanisms have not been determined.

Activation of Oxytocin Receptors Excites Subicular Neurons by Multiple Signaling and Ionic Mechanisms.

Oxytocin (OXT) is a nonapeptide that serves as a neuromodulator in the brain and a hormone participating in parturition and lactation in the periphery. The subiculum is the major output region of the hippocampus and an integral component in the networks that process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whilst the subiculum expresses the highest OXT-binding sites and is the first brain region to be activated by peripheral application of OXT, the precise actions of OXT in the subiculum have not been determined.

Oxytocin receptors excite lateral nucleus of central amygdala by phospholipase Cβ- and protein kinase C-dependent depression of inwardly rectifying K channels.

Key Points: Activation of oxytocin receptors (OXTRs) facilitates neuronal excitability in rat lateral nucleus of central amygdala (CeL). OXTR-induced excitation is mediated by inhibition of inwardly rectifying K (Kir) channels. Phospholipase Cβ is necessary for OXTR-mediated excitation of CeL neurons and depression of Kir channels.

Roles of K and cation channels in ORL-1 receptor-mediated depression of neuronal excitability and epileptic activities in the medial entorhinal cortex.

Nociceptin (NOP) is an endogenous opioid-like peptide that selectively activates the opioid receptor-like (ORL-1) receptors. The entorhinal cortex (EC) is closely related to temporal lobe epilepsy and expresses high densities of ORL-1 receptors. However, the functions of NOP in the EC, especially in modulating the epileptiform activity in the EC, have not been determined.

A protocol for preparation and transfection of rat entorhinal cortex organotypic cultures for electrophysiological whole-cell recordings.

Understanding how neuromodulators influence synaptic transmission and intrinsic excitability within the entorhinal cortex (EC) is critical to furthering our understanding of the molecular and cellular aspects of this region. Organotypic cultures can provide a cost-effective means to employ selective molecular biological strategies in elucidating cellular mechanisms of neuromodulation in the EC. We therefore adapted our acute slice model for organotypic culture applications and optimized a protocol for the preparation and biolistic transfection of cultured horizontal EC slices.

Somatostatin depresses the excitability of subicular bursting cells: Roles of inward rectifier K channels, KCNQ channels and Epac.

The hippocampus is a crucial component for cognitive and emotional processing. The subiculum provides much of the output for this structure but the modulation and function of this region is surprisingly under-studied. The neuromodulator somatostatin (SST) interacts with five subtypes of SST receptors (sst to sst ) and each of these SST receptor subtypes is coupled to Gi proteins resulting in inhibition of adenylyl cyclase (AC) and decreased level of intracellular cAMP.

Inhibition of L-Type Ca Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons.

Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1, mice.

Histamine facilitates GABAergic transmission in the rat entorhinal cortex: Roles of H and H receptors, Na -permeable cation channels, and inward rectifier K channels.

In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception, and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H , H , and H ).

TRPM2 Promotes Neurotoxin MPP/MPTP-Induced Cell Death.

In neurons, Ca is essential for a variety of physiological processes that regulate gene transcription to neuronal growth and their survival. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ions (MPP) are potent neurotoxins that selectively destroys the dopaminergic (DA) neurons and mimics Parkinson's disease (PD) like symptoms, but the mechanism as how MPP/MPTP effects DA neuron survival is not well-understood. In the present study, we found that MPP treatment increased the level of reactive oxygen species (ROS) that activates and upregulates the expression and function of melastatin-like transient receptor potential (TRPM) subfamily member, melastatin-like transient receptor potential channel 2 (TRPM2).

Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca²⁺ channels, calmodulin and myosin light-chain kinase.

Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer's disease, schizophrenia and Parkinson's disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats.

Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex.

Whereas the ionotropic glutamate receptors are the major mediator in glutamatergic transmission, the metabotropic glutamate receptors (mGluRs) usually play a modulatory role. Whereas the entorhinal cortex (EC) is an essential structure involved in the generation and propagation of epilepsy, the roles and mechanisms of mGluRs in epilepsy in the EC have not been determined. Here, we studied the effects of activation of group II metabotropic glutamate receptors (mGluRs II) on epileptiform activity induced by picrotoxin or deprivation of extracellular Mg2+ and neuronal excitability in the medial EC.

Neurotensinergic Excitation of Dentate Gyrus Granule Cells via Gαq-Coupled Inhibition of TASK-3 Channels.

Neurotensin (NT) is a 13-amino acid peptide and serves as a neuromodulator in the brain. Whereas NT has been implicated in learning and memory, the underlying cellular and molecular mechanisms are ill-defined. Because the dentate gyrus receives profound innervation of fibers containing NT and expresses high density of NT receptors, we examined the effects of NT on the excitability of dentate gyrus granule cells (GCs).

Cross interaction of dopaminergic and adrenergic systems in neural modulation.

Catecholamines including dopamine (DA) and norepinephrine (NE) are widely distributed in the body and exert extensive physiological functions by serving as neurotransmitters or neuromodulators. Alterations in the level of these two catecholamines underlie many neurological and psychiatric disorders. The pharmacology of both DA and NE including their individual receptors, signaling mechanisms, agonists and antagonists has been extensively studied.

Activation of neurotensin receptor 1 facilitates neuronal excitability and spatial learning and memory in the entorhinal cortex: beneficial actions in an Alzheimer's disease model.

Neurotensin (NT) is a tridecapeptide distributed in the CNS, including the entorhinal cortex (EC), a structure that is crucial for learning and memory and undergoes the earliest pathological alterations in Alzheimer's disease (AD). Whereas NT has been implicated in modulating cognition, the cellular and molecular mechanisms by which NT modifies cognitive processes and the potential therapeutic roles of NT in AD have not been determined. Here we examined the effects of NT on neuronal excitability and spatial learning in the EC, which expresses high density of NT receptors.

Corticotropin-releasing factor facilitates epileptiform activity in the entorhinal cortex: roles of CRF2 receptors and PKA pathway.

Whereas corticotropin-releasing factor (CRF) has been considered as the most potent epileptogenic neuropeptide in the brain, its action site and underlying mechanisms in epilepsy have not been determined. Here, we found that the entorhinal cortex (EC) expresses high level of CRF and CRF2 receptors without expression of CRF1 receptors. Bath application of CRF concentration-dependently increased the frequency of picrotoxin (PTX)-induced epileptiform activity recorded from layer III of the EC in entorhinal slices although CRF alone did not elicit epileptiform activity.

Bombesin facilitates GABAergic transmission and depresses epileptiform activity in the entorhinal cortex.

Bombesin and the bombesin-like peptides including neuromedin B (NMB) and gastrin-releasing peptide (GRP) are important neuromodulators in the brain. We studied their effects on GABAergic transmission and epileptiform activity in the entorhinal cortex (EC). Bath application of bombesin concentration-dependently increased both the frequency and amplitude of sIPSCs recorded from the principal neurons in the EC.

Dopaminergic modulation of GABAergic transmission in the entorhinal cortex: concerted roles of α1 adrenoreceptors, inward rectifier K⁺, and T-type Ca²⁺ channels.

Whereas the entorhinal cortex (EC) receives profuse dopaminergic innervations from the midbrain, the effects of dopamine (DA) on γ-Aminobutyric acid (GABA)ergic interneurons in this brain region have not been determined. We probed the actions of DA on GABAA receptor-mediated synaptic transmission in the EC. Application of DA increased the frequency, not the amplitude, of spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) recorded from entorhinal principal neurons, but slightly reduced the amplitude of the evoked IPSCs.