No description available.

Memory stabilization following encoding (synaptic consolidation) or memory reactivation (reconsolidation) requires gene expression and protein synthesis. Although consolidation and reconsolidation may be mediated by distinct molecular mechanisms, disrupting the function of the transcription factor CREB (cAMP responsive element binding protein) impairs both processes. We use a gain-of-function approach to show that CREB (and CREB-coactivator CRTC1) can facilitate both synaptic and systems consolidation and reconsolidation. We first examine whether acutely increasing CREB levels in the dorsal hippocampus is sufficient to enhance spatial memory formation in the watermaze. Locally and acutely increasing CREB in the dorsal hippocampus using viral vectors is sufficient to induce robust spatial memory in two conditions which do not normally support consolidation, weakly-trained wild-type (WT) mice and strongly-trained mutant mice with brain-wide disrupted CREB function. CRTCs (CREB regulated transcription co-activators) are a powerful co-activator of CREB, but their role in memory is virtually unexplored. We show, for the first time, that the novel CREB co-activator CRTC1 enhances memory consolidation. Locally increasing CRTC1 (or CREB) in the dorsal hippocampus of WT mice prior to weak context fear conditioning facilitates consolidation of precise context memory. Last, we show that CREB or CRTC1 facilitates precise and enduring memory consolidation and reconsolidation. Acute enhancement of hippocampal CREB or CRTC1 during initial synaptic consolidation can maintain precision of remote context memory, while increasing CREB or CRTC1 just prior to reactivation of a weak remote context memory enhances context memory reconsolidation. These gain-of-function manipulations indicate that increasing CRTC1 or CREB function is sufficient to enhance the strength of new, as well as reactivated established, memories without compromising memory specificity. Together with previous results, these findings indicate that CREB is both necessary and sufficient for hippocampal-dependent memory formation, and underline its pivotal role in the hippocampal molecular machinery underlying long-term memory consolidation and reconsolidation.

Memory stabilization following encoding (synaptic consolidation) or memory reactivation (reconsolidation) requires gene expression and protein synthesis. Although consolidation and reconsolidation may be mediated by distinct molecular mechanisms, disrupting the function of the transcription factor CREB (cAMP responsive element binding protein) impairs both processes. We use a gain-of-function approach to show that CREB (and CREB-coactivator CRTC1) can facilitate both synaptic and systems consolidation and reconsolidation. We first examine whether acutely increasing CREB levels in the dorsal hippocampus is sufficient to enhance spatial memory formation in the watermaze. Locally and acutely increasing CREB in the dorsal hippocampus using viral vectors is sufficient to induce robust spatial memory in two conditions which do not normally support consolidation, weakly-trained wild-type (WT) mice and strongly-trained mutant mice with brain-wide disrupted CREB function. CRTCs (CREB regulated transcription co-activators) are a powerful co-activator of CREB, but their role in memory is virtually unexplored. We show, for the first time, that the novel CREB co-activator CRTC1 enhances memory consolidation. Locally increasing CRTC1 (or CREB) in the dorsal hippocampus of WT mice prior to weak context fear conditioning facilitates consolidation of precise context memory. Last, we show that CREB or CRTC1 facilitates precise and enduring memory consolidation and reconsolidation. Acute enhancement of hippocampal CREB or CRTC1 during initial synaptic consolidation can maintain precision of remote context memory, while increasing CREB or CRTC1 just prior to reactivation of a weak remote context memory enhances context memory reconsolidation. These gain-of-function manipulations indicate that increasing CRTC1 or CREB function is sufficient to enhance the strength of new, as well as reactivated established, memories without compromising memory specificity. Together with previous results, these findings indicate that CREB is both necessary and sufficient for hippocampal-dependent memory formation, and underline its pivotal role in the hippocampal molecular machinery underlying long-term memory consolidation and reconsolidation.

[pt] A matéria cinzenta periaquedutal dorsal (MCPD) é associada com comportamento defensivo e ataques de pânico em humanos. Estimulações elétricas ou farmacológicas da MCPD induzem a reações aversivas de corrida e pulo em ratos. Os resultados no experimento 1 indicaram que animais submetidos a um contexto previamente associado com choques nas patas, obtiveram um comportamento defensivo de congelamento robusto e tiveram menores reações defensivas de corridas e pulos através da microinjeção de de 0.3 µl N-metil-D- aspartato (NMDA; 15.0 mg/kg), quando comparado com o grupo controle que não foi exposto ao procedimento de medo ao contexto. No experimento 2, o efeito de injeções de pentilenotetrazol (PTZ; 15.0 mg/kg i.p.) em ratos microinjetados com NMDA nas reações de corridas e pulos foi investigado. Os resultados mostraram que o PTZ (1ml/100gr) foi capaz de minimizar as reações aversivas de corridas e pulos induzidas pela microinjeção de NMDA na MCPD. Esses resultados sugerem que a ativação de mecanismos cerebrais que permeiam a ansiedade produzem um efeito inibitório em ataques de pânico. / [en] The dorsal portion of the periaqueductal gray (DPAG) is notably associated with defensive behavior and panic attacks in humans. Electrical or pharmacological stimulation of the DPAG induces aversive reactions such as running and jumping in rats. Our results indicate that animals exposed to contextual cues, that were previously associated with electrical footshocks, engaged in robust defensive freezing behavior and were less likely to display running and jumping defensive reactions by microinjection of 0.3 µl N-methyl-D-aspartate (NMDA; 15.0 mg/kg) into DPAG when compared with control animals that were not exposed to the context fear conditioning procedure. Furthermore the effect of pentylenotetrazole injections (PTZ; 15.0 mg/kg i.p.) in microinjected NMDA rats in aversive reactions of running and jumping was investigated. The result showed that PTZ dose (1ml/100gr) was capable to minimize the aversive reactions of running and jumping induced by microinjection of NMDA into DPAG. These results suggest that activation of the brain mechanisms that underlie anxiety produces an inhibitory effect on panic attacks.