Biomedical subjects

Nicole Mons

Publications and source records attributed to Nicole Mons.

6 recordsLinked to original sources

PubMed2006

Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response.

Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.

Acetylcholine↗

PubMed2006

Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation.

Fear conditioning is a popular model for investigating physiological and cellular mechanisms of memory formation. In this paradigm, a footshock is either systematically associated to a tone (paired conditioning) or is pseudorandomly distributed (unpaired conditioning). In the former procedure, the tone/shock association is acquired, whereas in the latter procedure, the context/shock association will prevail. Animals with chronically implanted recording electrodes show enhanced amplitude of the extracellularly recorded field EPSP in CA1 pyramidal cells for up to 24 h after unpaired, but not paired, fear conditioning. This is paralleled by a differential activation of the ERK/CREB pathway in CA1, which is monophasic in paired conditioning (0-15 min post-conditioning), but biphasic (0-1 h and 9-12 h post-conditioning) in unpaired conditioning as revealed by immunocytochemistry and Western blotting. Intrahippocampal injection of the MEK inhibitor U0126 prior to each phase prevents the activation of both ERK1/2 and CREB after unpaired conditioning. Block of any activation phase leads to memory impairment. We finally reveal that the biphasic activation of ERK/CREB activity is independently regulated, yet both phases are critically required for the consolidation of long-term memories following unpaired fear conditioning. These data provide compelling evidence that CA1 serves different forms of memory by expressing differential cellular mechanisms that are dependent on the training regime.

Animals↗

PubMed2006

Extinction of auditory fear conditioning requires MAPK/ERK activation in the basolateral amygdala.

Whereas the neuronal substrates underlying the acquisition of auditory fear conditioning have been widely studied, the substrates and mechanisms mediating the acquisition of fear extinction remain largely elusive. Previous reports indicate that consolidation of fear extinction depends on the mitogen-activated protein kinase/extracellular-signal regulated kinase (MAPK/ERK) signalling pathway and on protein synthesis in the medial prefrontal cortex (mPFC). Based on experiments using the fear-potentiated startle paradigm suggesting a role for neuronal plasticity in the basolateral amygdala (BLA) during fear extinction, we directly addressed whether MAPK/ERK signalling in the basolateral amygdala is necessary for the acquisition of fear extinction using conditioned freezing as a read-out. First, we investigated the regional and temporal pattern of MAPK/ERK activation in the BLA following extinction learning in C57Bl/6J mice. Our results indicate that acquisition of extinction is associated with an increase of phosphorylated MAPK/ERK in the BLA. Moreover, we found that inhibition of the MAPK/ERK signalling pathway by intrabasolateral amygdala infusion of the MEK inhibitor, U0126, completely blocks acquisition of extinction. Thus, our results indicate that the MAPK/ERK signalling pathway is required for extinction of auditory fear conditioning in the BLA, and support a role for neuronal plasticity in the BLA during the acquisition of fear extinction.

Acoustic Stimulation↗

PubMed2004

Resistance to extinction is associated with impaired immediate early gene induction in medial prefrontal cortex and amygdala.

Extinction of classical fear conditioning is thought to involve activity-dependent potentiation of synaptic transmission in the medial prefrontal cortex (mPFC), resulting in the inhibition of amygdala-dependent fear responses. While many studies have addressed the mechanisms underlying extinction learning, it is unclear what determines whether extinction memory is consolidated or whether spontaneous recovery of the fear response occurs. Here we show, using a combined electrophysiological and immunocytochemical approach, that spontaneous recovery of conditioned fear in mice is associated with a prolonged expression of long-term depression of synaptic transmission in the mPFC and the failure of induction of the immediate-early genesc-Fos and zif268 in the mPFC and the basolateral nucleus of the amygdala. This suggests that coordinated activity-dependent changes in gene expression in the mPFC and the amygdala may underlie the formation of long-term fear extinction memory.

Amygdala↗

PubMed2003

Chronic ethanol consumption restores the age-related decrease in neurogranin mRNA level in the hippocampus of mice.

Neurogranin (Ng) is a Ca(2+)-sensitive calmodulin-binding neuron-specific protein that has been implicated in the regulation of numerous post-synaptic signalling pathways. Here, we investigate the effects of 5 months low level ethanol consumption (approximately 20% of total calories intake) on Ng mRNA expression in the brain of adult (approximately 7-8 months) and aged (approximately 21-22 months) mice using in situ hybridization histochemistry. Results showed that ageing was accompanied by a decrease in amounts of mRNA coding for Ng, especially in the hippocampus (approximately 25% of adults) known to play a critical role in higher cognitive functions. Chronic ethanol consumption restored this decline up to pre-senescent (adult) levels without altering Ng mRNA levels in adult mice. On the basis of recent data indicating a central role for Ng in the regulation of hippocampal synaptic plasticity and spatial learning, our results suggest that moderate ethanol consumption might have a beneficial influence on cognitive deterioration during senescence. Such a possibility is in fact congruent with recent follow-up studies conducted in elderly people.

Aging↗

PubMedDate not supplied

CREB antisense oligodeoxynucleotide administration into the dorsal hippocampal CA3 region impairs long- but not short-term spatial memory in mice.

The transcription factor cAMP response-element binding protein (CREB) has a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent long-term memory. We recently demonstrated that the dorsal hippocampal CA3 region is involved in memory consolidation of spatial information tested on a Morris water maze in mice. To test whether activation of CREB in the CA3 region is required for memory consolidation of spatial information, bilaterally cannulated mice were infused 18 h before the beginning of the behavioral training with antisense or control sense CREB oligodeoxynucleotides (ODNs) or buffer. Mice were then subjected to massed training in a spatial version of the water maze and tested for retention 0 or 24 h after the last training session. We showed that CREB antisense ODN-infusion in the CA3 region impaired long-term memory when tested 24 h later but had no effect on spatial acquisition or short-term memory tested immediately after behavioral training. These findings provide evidence that the regionally restricted activation of CREB in the dorsal hippocampal CA3 region is critical for the long-term memory consolidation phase of spatial learning but not for short-term memory.

Animals↗