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ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X andmetabotropic P2Y receptors and subsequentmodulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain.We show that P2Y receptors inhibit the release of neurotransmitters,modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed heremay explain howP2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, orAlzheimer’s disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states. [ABSTRACT FROM AUTHOR]

Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals. [ABSTRACT FROM AUTHOR]

CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel-mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. [ABSTRACT FROM AUTHOR]

Abstract: Long-term depression (LTD) is a form of synaptic plasticity that may contribute to information storage in the central nervous system. Here we report that LTD can be elicited in layer 5 pyramidal neurons of the rat prefrontal cortex by pairing low frequency stimulation with a modest postsynaptic depolarization. The induction of LTD required the activation of both metabotropic glutamate receptors of the mGlu1 subtype and voltage-sensitive Ca2+ channels (VSCCs) of the T/R, P/Q and N types, leading to the stimulation of intracellular inositol trisphosphate (IP3) receptors by IP3 and Ca2+. The subsequent release of Ca2+ from intracellular stores activated the protein phosphatase cascade involving calcineurin and protein phosphatase 1. The activation of purinergic P2Y1 receptors blocked LTD. This effect was prevented by P2Y1 receptor antagonists and was absent in mice lacking P2Y1 but not P2Y2 receptors. We also found that activation of P2Y1 receptors inhibits Ca2+ transients via VSCCs in the apical dendrites and spines of pyramidal neurons. In addition, we show that the release of ATP under hypoxia is able to inhibit LTD by acting on postsynaptic P2Y1 receptors. In conclusion, these data suggest that the reduction of Ca2+ influx via VSCCs caused by the activation of P2Y1 receptors by ATP is the possible mechanism for the inhibition of LTD in prefrontal cortex. [ABSTRACT FROM AUTHOR]

A recent paper by von Engelhardt et al. identifies a novel auxiliary subunit of native AMPARs, termed CKAMP44. Unlike other auxiliary subunits, CKAMP44 accelerates desensitization and prolongs recovery from desensitization. CKAMP44 is highly expressed in hippocampal dentate gyrus granule cells and decreases the paired-pulse ratio at perforant path input synapses. Thus, both principal and auxiliary AMPAR subunits control the time course of signaling at glutamatergic synapses. [Copyright &y& Elsevier]

Long-term depression (LTD) is a form of synaptic plasticity that may contribute to information storage in the central nervous system. Here we report that LTD can be elicited in layer 5 pyramidal neurons of the rat prefrontal cortex by pairing low frequency stimulation with a modest postsynaptic depolarization. The induction of LTD required the activation of both metabotropic glutamate receptors of the mGlu1 subtype and voltage-sensitive Ca(2+) channels (VSCCs) of the T/R, P/Q and N types, leading to the stimulation of intracellular inositol trisphosphate (IP3) receptors by IP3 and Ca(2+). The subsequent release of Ca(2+) from intracellular stores activated the protein phosphatase cascade involving calcineurin and protein phosphatase 1. The activation of purinergic P2Y(1) receptors blocked LTD. This effect was prevented by P2Y(1) receptor antagonists and was absent in mice lacking P2Y(1) but not P2Y(2) receptors. We also found that activation of P2Y(1) receptors inhibits Ca(2+) transients via VSCCs in the apical dendrites and spines of pyramidal neurons. In addition, we show that the release of ATP under hypoxia is able to inhibit LTD by acting on postsynaptic P2Y(1) receptors. In conclusion, these data suggest that the reduction of Ca(2+) influx via VSCCs caused by the activation of P2Y(1) receptors by ATP is the possible mechanism for the inhibition of LTD in prefrontal cortex., (Copyright © 2010 Elsevier Ltd. All rights reserved.)