Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal

The orbitofrontal cortex is involved in the reinforcing effects of drugs of abuse. However, how the dynamic activity in OFC changes during opiate administration and withdrawal period has not been investigated. We first tested the effects of opiates and dr

Spatially directed movement and neuronal activity in freely moving monkey

The abilities to plan a series of movements and to navigate within the environment require the functions of the frontal and ventromedial temporal lobes, respectively. Neuropsychological studies posit the existence of egocentric (prefrontal) and allocentri

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement t

Distracters Impair and Create Working Memory-Related Neuronal Activity in the Prefrontal Cortex

The prefrontal cortex (PFC) has a central role in working memory (WM). Resistance to distraction is considered a fundamental feature of WM and PFC neuronal activity. However, although unexpected stimuli often disrupt our work, little is known about the un

Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death

Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASICla-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca2+ elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis.