BDNF-dependent signaling in the olfactory bulb modulates social recognition memory in mice.

An operative olfactory bulb (OB) is critical to social recognition memory (SRM) in rodents, which involves identifying conspecifics. Furthermore, OB also allocates synaptic plasticity events related to olfactory memories in their intricate neural circuit. Here, we asked whether the OB is a target for brain-derived neurotrophic factor (BDNF), a well-known mediator of plasticity and memory. Adult ICR-CD1 male mice had their SRM evaluated under the inhibition of BDNF-dependent signaling directly in the OB. We also quantified the expression of BDNF in the OB, after SRM acquisition. Our results presented an amnesic effect of anti-BDNF administered 12 h post-training. Although the western blot showed no statistical difference in pro-BDNF and BDNF expression, the analysis of fluorescence intensity in slices suggests SRM acquisition decreases BDNF in the granular cell layer of the OB. Next, to test the ability of BDNF to rescue SRM deficit, we administered the human recombinant BDNF (rBDNF) directly in the OB of socially isolated (SI) mice. Unexpectedly, rBDNF did not rescue SRM in SI mice. Furthermore, BDNF and pro-BDNF expression in the OB was unchanged by SI. Our study reinforces the OB as a plasticity locus in memory-related events. It also adds SRM as another type of memory sensitive to BDNF-dependent signaling.

Social isolation impairs the persistence of social recognition memory by disturbing the glutamatergic tonus and the olfactory bulb-dorsal hippocampus coupling.

The absence of companion may jeopardize mental health in social animals. Here, we tested the hypothesis that social isolation impairs social recognition memory by altering the excitability and the dialog between the olfactory bulb (OB) and the dorsal hippocampus (dHIP). Adult male Swiss mice were kept grouped (GH) or isolated (SI) for 7 days. Social memory (LTM) was evaluated using social recognition test. SI increased glutamate release in the OB, while decreased in the dHIP. Blocking AMPA and NMDA receptors into the OB or activating AMPA into the dHIP rescued LTM in SI mice, suggesting a cause-effect relationship between glutamate levels and LTM impairment. Additionally, during memory retrieval, phase-amplitude coupling between OB and dHIP decreased in SI mice. Our results indicate that SI impaired the glutamatergic signaling and the normal communication between OB and HIP, compromising the persistence of social memory.

Hippocampus and Prefrontal Cortex Modulation of Contextual Fear Memory Is Dissociated by Inhibiting De Novo Transcription During Late Consolidation.

To uncover the factors that dictate the persistence of a memory, it is critical to determine the molecular basis of consolidation. Here, we submitted male adult C57/BL6 mice to contextual fear conditioning using 1US (US: foot-shock, 0.7 mA, 2 s) or 5US, to generate recent (24 to 48 h) and remote (30 days) memories, respectively. To access the functional role of de novo transcription, we injected actinomycin D (ActD: 2.5 ng/side) directly into the dorsal hippocampus (HIP) or dorsomedial prefrontal cortex (dmPFC), 0 (early consolidation) or 12 h (late consolidation) after training. Our results showed that de novo transcription at 0 h was required for recent and remote memories. However, 12 h was a critical time point to memory persistence. In the dHIP, de novo transcription at 12 h post-training differentiated the recent memory from the remote. In the dmPFC, ActD affected memory formation depending on the training intensity (1 or 5US). Specifically, freezing was amplified after 5US conditioning. Furthermore, inhibiting de novo transcription at 12 h post-training in the dmPFC rapidly increased c-Fos expression in the amygdala. Altogether, our results indicate that contextual fear memory duration is particularly sensitive to de novo transcription in the dHIP and dmPFC, at a specific time point of late consolidation.