J. Neurochem. (2010) 112, 636–650.
Abstract
Most recent studies aimed at defining the cellular and molecular mechanisms of Pavlovian fear conditioning have focused on protein kinase signaling pathways and the transcription factor cAMP‐response element binding protein (CREB) that promote fear memory consolidation in the lateral nucleus of the amygdala (LA). Despite this progress, there still remains a paucity of information regarding the genes downstream of CREB that are required for long‐term fear memory formation in the LA. We have adopted a strategy of using microarray technology to initially identify genes induced within the dentate gyrus following in vivo long‐term potentiation (LTP) followed by analysis of whether these same genes are also regulated by fear conditioning within the LA. In the present study, we first identified 34 plasticity‐associated genes that are induced within 30 min following LTP induction utilizing a combination of DNA microarray, qRT‐PCR, and in situ hybridization. To determine whether these genes are also induced in the LA following Pavlovian fear conditioning, we next exposed rats to an auditory fear conditioning protocol or to control conditions that do not support fear learning followed by qRT‐PCR on mRNA from microdissected LA samples. Finally, we asked whether identified genes induced by fear learning in the LA are downstream of the extracellular‐regulated kinase/mitogen‐activated protein kinase signaling cascade. Collectively, our findings reveal a comprehensive list of genes that represent the first wave of transcription following both LTP induction and fear conditioning that largely belong to a class of genes referred to as ‘neuronal activity dependent genes’ that are likely calcium, extracellular‐regulated kinase/mitogen‐activated protein kinase, and CREB‐dependent.
Prepulse inhibition (PPI) is the reduction of the startle reflex when the startling stimulus is shortly preceded by a non-startling stimulus. Previous studies have shown that PPI in rats can be enhanced by auditory fear conditioning (AFC) but weakened by isolation rearing. This study investigated whether isolation rearing affects the effect of AFC on PPI. The results show that PPI was lower in isolation-reared rats than that in socially reared rats, and it was markedly enhanced by AFC in socially reared rats. However, the AFC-induced PPI enhancement in isolation-reared rats was much lower than that in socially reared rats. Moreover, the AFC-induced PPI enhancement was blocked by intraperitoneal injection (1 mg/kg) of the selective antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP), 30 minutes before AFC. The baseline startle was also enhanced by isolation rearing. Thus, isolation rearing impairs not only PPI but also the AFC-induced PPI enhancement, which depends on mGluR5 activity. This study advances the animal model for investigating both neural bases and cognitive features of schizophrenia.
Auditory frequency-following responses (FFRs) are sustained potentials based on phase-locked neural activity preserving low-frequency information. Some neurons in rat inferior colliculus are excited by stimuli at either ear. This study shows that FFRs in inferior colliculus can be elicited by presenting pure tone bursts with frequencies from 225 to 4025 Hz at the ipsilateral ear in anesthetized rats. Moreover, chemical block of glutamate transmissions in the contralateral inferior colliculus markedly reduced the ipsilaterally driven FFRs, which, however, were significantly enhanced by blocking the contralateral dorsal nucleus of the lateral lemniscus. Thus, FFRs in inferior colliculus to ipsilateral stimulation were facilitated by excitatory projections from the contralateral inferior colliculus but suppressed by inhibitory projections from the contralateral dorsal nucleus of the lateral lemniscus.
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