Much data implicates the amygdala in the expression and learning of fear. Yet, few studies have examined the neuronal correlates of fear in the amygdala. This study aimed to determine whether fear is correlated to particular activity patterns in the lateral amygdaloid (LA) nucleus. Cats, chronically implanted with multiple microelectrodes in the LA and a catheter in the femoral artery, learned that a series of tones interrupted by a period of silence (5 sec) preceded the administration of a footshock. During the silent period, their blood pressure increased, indicating that they anticipated the noxious stimulus. In parallel, the firing rate of LA neurons doubled, and the discharges of simultaneously recorded cells became more synchronized. Moreover, cross-correlation of focal LA waves revealed a significant increase in synchrony restricted to the theta band. In keeping with this, perievent histograms of neuronal discharges revealed rhythmic changes in the firing probability of LA neurons in relation to focal theta waves. Finally, the responsiveness of LA cells to the stimuli predicting the footshock (the tones) increased during the trials, whereas responses to unrelated stimuli (perirhinal shocks) remained stable. Thus, during the anticipation of noxious stimuli, a state here defined anthropomorphically as fear, the firing rate of LA neurons increases, and their discharges become more synchronized through a modulation at the theta frequency. The presence of theta oscillations in the LA might facilitate cooperative interactions between the amygdala and cortical areas involved in memory.

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SummaryNeuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.