Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation.

Long-term potentiation (LTP) in the rat hippocampus is the most extensively studied cellular model for learning and memory. Induction of classical LTP involves an NMDA-receptor- and calcium-dependent increase in functional synaptic AMPA receptors, mediated by enhanced recycling of internalized AMPA receptors back to the postsynaptic membrane. Here we report a physiologically relevant NMDA-receptor-independent mechanism that drives increased AMPA receptor recycling and LTP.

Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models.

Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. Yet, it remains unclear how the HTT mutation affects NMDAR function, and direct evidence for a causative role is missing.

Homeostatic synaptic scaling is regulated by protein SUMOylation.

Homeostatic scaling allows neurons to alter synaptic transmission to compensate for changes in network activity. Here, we show that suppression of network activity with tetrodotoxin, which increases surface expression of AMPA receptors (AMPARs), dramatically reduces levels of the deSUMOylating (where SUMO is small ubiquitin-like modifier) enzyme SENP1, leading to a consequent increase in protein SUMOylation. Overexpression of the catalytic domain of SENP1 prevents this scaling effect, and we identify Arc as a SUMO substrate involved in the tetrodotoxin-induced increase in AMPAR surface expression.

Inhibition of post-synaptic Kv7/KCNQ/M channels facilitates long-term potentiation in the hippocampus.

Activation of muscarinic acetylcholine receptors (mAChR) facilitates the induction of synaptic plasticity and enhances cognitive function. In the hippocampus, M(1) mAChR on CA1 pyramidal cells inhibit both small conductance Ca(2+)-activated KCa2 potassium channels and voltage-activated Kv7 potassium channels. Inhibition of KCa2 channels facilitates long-term potentiation (LTP) by enhancing Ca(2+)calcium influx through postsynaptic NMDA receptors (NMDAR).

Facilitation of long-term potentiation by muscarinic M(1) receptors is mediated by inhibition of SK channels.

Muscarinic receptor activation facilitates the induction of synaptic plasticity and enhances cognitive function. However, the specific muscarinic receptor subtype involved and the critical intracellular signaling pathways engaged have remained controversial. Here, we show that the recently discovered highly selective allosteric M(1) receptor agonist 77-LH-28-1 facilitates long-term potentiation (LTP) induced by theta burst stimulation at Schaffer collateral synapses in the hippocampus.

Properties of thiamine transport in isolated perfused hearts of chronically alcoholic guinea pigs.

The aim of this study was to determine the mechanism of transport of (14)C-thiamine in the hearts of healthy (nonalcoholic) and chronically alcoholic guinea pigs. We used the single-pass, paired-tracer dilution method on isolated and retrogradely perfused guinea pig hearts. The maximal cellular uptake (U(max)) and total cellular uptake (U(tot)) of (14)C-thiamine were determined under control conditions and under influence of possible modifiers.