Pavlovian fear memory induced by activation in the anterior cingulate cortex

Identifying higher brain central region(s) that are responsible for the unpleasantness of pain is the focus of many recent studies. Here we show that direct stimulation of the anterior cingulate cortex (ACC) in mice produced fear-like freezing responses and induced long-term fear memory, including contextual and auditory fear memory. Auditory fear memory required the activation of N-methyl-D-aspartate (NMDA) receptors in the amygdala. To test the hypothesis that neuronal activity in the ACC contributes to unpleasantness, we injected a GABA(A )receptor agonist, muscimol bilaterally into the ACC. Both contextual and auditory memories induced by foot shock were blocked. Furthermore, activation of metabotropic glutamate receptors in the ACC enhanced behavioral escape responses in a noxious hot-plate as well as spinal nociceptive tail-flick reflex. Our results provide strong evidence that the excitatory activity in the ACC contribute to pain-related fear memory as well as descending facilitatory modulation of spinal nociception

Stability of recent and remote contextual fear memory

Following initial encoding, memories undergo a prolonged period of reorganization. While such reorganization may occur in many different memory systems, its purpose is not clear. Previously, we have shown that recall of recent contextual fear memories engages the dorsal hippocampus (dHPC). In contrast, recall of remote contextual fear memories engages a number of different cortical regions, including the anterior cingulate cortex (ACC). To examine whether this reorganization leads to greater memory stability, we examined reconsolidation of 1 d-old (recent) and 36 d-old (remote) contextual fear memory in mice. We infused the protein synthesis inhibitor, anisomycin (ANI), into either the dHPC or ACC immediately following retrieval of either a recent or remote contextual fear memory. In the dHPC, ANI infusions disrupted subsequent expression of recent, but not remote, contextual fear memory. Similar infusions into the ACC had no effect on either recent or remote contextual fear memories, whereas systemically applied ANI blocked subsequent remote memory expression when long re-exposure durations were used. Together, these data suggest that as memories mature they become increasingly stable. Furthermore, the dissociation between the effects of systemically and centrally administered ANI on remote memory suggests that stability is due, in part, to the distributed nature of remote contextual fear memories

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex

Amyloid ? (A?) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of A?-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents A?-induced impairment of LTP. Moreover, we show that A? increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by A? and prevents A?-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for A? to impair synaptic plasticity in the hippocampus and suggest that the A?-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between A? and tau could be a promising strategy for treating cognitive impairment in MCI and early AD. <br/