MeCP2 in cholinergic interneurons of nucleus accumbens regulates fear learning.

Methyl-CpG-binding protein 2 (MeCP2) encoded by the gene is a transcriptional regulator whose mutations cause Rett syndrome (RTT). -deficient mice show fear regulation impairment; however, the cellular and molecular mechanisms underlying this abnormal behavior are largely uncharacterized. Here, we showed that gene deficiency in cholinergic interneurons of the nucleus accumbens (NAc) dramatically impaired fear learning.

Substance P inhibits GABAB receptor signalling in the ventral tegmental area.

Substance P (SP) and its receptors are involved in anxiety-related behaviours and regulate the intake of drugs of abuse and alcohol. Within the midbrain ventral tegmental area (VTA), a region that is clearly involved in the control of these behaviours, SP is released by stress and has been shown to trigger relapse. SP activates neurokinin (NK) receptors, which excites midbrain dopamine (DA) neurons and leads to increased DA in target regions.

Increased Ca2+ influx through Na+/Ca2+ exchanger during long-term facilitation at crayfish neuromuscular junctions.

Intense motor neuron activity induces a long-term facilitation (LTF) of synaptic transmission at crayfish neuromuscular junctions (NMJs) that is accompanied by an increase in the accumulation of presynaptic Ca2+ ions during a test train of action potentials. It is natural to assume that the increased Ca2+ influx during action potentials is directly responsible for the increased transmitter release in LTF, especially as the magnitudes of LTF and increased Ca2+ influx are positively correlated. However, our results indicate that the elevated Ca2+ entry occurs through the reverse mode operation of presynaptic Na+/Ca2+ exchangers that are activated by an LTF-inducing tetanus.

Acute amphetamine exposure selectively desensitizes kappa-opioid receptors in the nucleus accumbens.

In the present study, we investigated the effects of psychostimulant exposure on kappa-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.

Cancer metastasis-suppressing peptide metastin upregulates excitatory synaptic transmission in hippocampal dentate granule cells.

Metastin is an antimetastatic peptide encoded by the KiSS-1 gene in cancer cells. Recent studies found that metastin is a ligand for the orphan G-protein-coupled receptor GPR54, which is highly expressed in specific brain regions such as the hypothalamus and parts of the hippocampus. This study shows that activation of GPR54 by submicromolar concentrations of metastin reversibly enhances excitatory synaptic transmission in hippocampal dentate granule cells in a mitogen-activated protein (MAP) kinase-dependent manner.

Positive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators have different impact on synaptic transmission in the thalamus and hippocampus.

Earlier studies showed that positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors enhance synaptic responses and facilitate synaptic plasticity. Those studies focused mainly on hippocampal functions. However, AMPA receptors have regionally distinct subunit compositions and thus potencies and efficacies of modulators may vary across the brain.

Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action.

CX516 (BDP-12) and CX546, two first-generation benzamide-type AMPA receptor modulators, were compared with regard to their influence on AMPA receptor-mediated currents, autaptic responses in cultured hippocampal neurons, hippocampal excitatory postsynaptic currents, synaptic field potentials, and agonist binding. The two drugs exhibited comparable potencies in most tests but differed in their efficacy and in their relative impact on various response parameters. CX546 greatly prolonged the duration of synaptic responses, and it slowed 10-fold the deactivation of excised-patch currents following 1-ms pulses of glutamate.

Effects of 5'-alkyl-benzothiadiazides on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses.

Alkyl-substituted benzothiadiazides (BTDs) were tested for their effects on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. In excised patches, the 5'-ethyl derivative "D1" blocked the desensitization of AMPA receptor currents during prolonged application of glutamate (EC(50), 36 microM), and it slowed deactivation of responses elicited by 1-ms glutamate pulses greater than 10-fold. [(3)H]Fluorowillardiine binding to rat synaptic membranes was increased by D1 by a factor of 3.