Temporal association activates projections from the perirhinal cortex and ventral CA1 to the prelimbic cortex and from the prelimbic cortex to the basolateral amygdala.

In trace fear conditioning, the prelimbic cortex exhibits persistent activity during the interval between the conditioned and unconditioned stimuli, which maintains a conditioned stimulus representation. Regions cooperating for this function or encoding the conditioned stimulus before the interval could send inputs to the prelimbic cortex, supporting learning. The basolateral amygdala has conditioned stimulus- and unconditioned stimulus-responsive neurons, convergently activated. The prelimbic cortex could directly project to the basolateral amygdala to associate the transient memory of the conditioned stimulus with the unconditioned stimulus. We investigated the neuronal circuit supporting temporal associations using contextual fear conditioning with a 5-s interval, in which 5 s separates the contextual conditioned stimulus from the unconditioned stimulus. Injecting retrobeads, we quantified c-Fos in prelimbic cortex- or basolateral amygdala-projecting neurons from 9 regions after contextual fear conditioning with a 5-s interval or contextual fear conditioning, in which the conditioned and unconditioned stimuli overlap. The contextual fear conditioning with a 5-s interval activated ventral CA1 and perirhinal cortex neurons projecting to the prelimbic cortex and prelimbic cortex neurons projecting to basolateral amygdala. Both fear conditioning activated ventral CA1 and lateral entorhinal cortex neurons projecting to basolateral amygdala and basolateral amygdala neurons projecting to prelimbic cortex. The perirhinal cortex â†’ prelimbic cortex and ventral CA1 â†’ prelimbic cortex connections are the first identified prelimbic cortex afferent projections participating in temporal associations. These results help to understand time-linked memories, a process required in episodic and working memories.

Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions.