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

Abstract

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.

Figure 1

Effect of social isolation on the release of glutamate in the (A) olfactory bulb and (B) hippocampus. (n = 4/group). Results expressed as mean ± standard error of the mean. *Indicates difference between groups.

Figure 2

Effect of NBQX (AMPA receptor antagonist) and AP5 (NMDA receptor antagonist) administration in the olfactory bulb (OB), immediately after the training session on the social recognition task. (A) Schematic representation of the experimental design. (B) Blockade of AMPA (NBQX) and NMDA (AP5) receptors into the OB recovered the social long-term memory (LTM) in social isolated (SI) mice without affecting social short-term memory (STM) (n = 6–12/group). (C) NBQX and AP5 into the OB did not affect STM and LTM in group-housed (GH) mice (n = 7–8/group). (D) AMPA and NMDA agonists impaired LTM in GH animals (n = 5–10/group). Results are expressed as mean ± standard error of the mean. *Indicates difference between the training and test sessions, within the same group.

Figure 3

Effect of AMPA and NMDA receptors agonists administration in the dorsal hippocampus (dHIP), immediately after the training session on the social recognition task. (A) Schematic representation of the experimental design. (B) AMPA agonist into the dHIP recovered the social long-term memory (LTM) deficit of social isolated mice (SI). NMDA agonist did not recover LTM (n = 7–8/group) of SI mice. (C) Administration of NBQX impairs the consolidation of LTM in group-housed animals (GH), while, the administration of AP5 did not affect LTM (n = 6–16/group). Results are expressed as mean ± standard error of the mean. *Indicates difference between the training and test sessions, within the same group.

Figure 4

Effect of social exploration on fast gamma and theta oscillations in the (C) olfactory bulb (OB) and (F) dorsal hippocampus (dHIP). Social exploration increases fast gamma power in the (A) OB (n = 6/group) and (D) dHIP (n = 5/group), in both groups. ^#Indicates difference between no exploration and social exploration within the same group. There was no difference in theta power after social exploration in (B) OB (n = 6/group) and (E) dHIP (n = 5/group) of both groups.

Figure 5

Effect of social isolation on the olfactory bulb gamma and theta oscillations, during social long-term memory retrieval (LTM). (A) Power Spectral Density (PSD) from one representative animal from group-housed (dark lines) and social isolated (grey lines) groups. (B) Theta and (C) fast gamma power during LTM. *Indicates difference between groups. Correlation between LTM performance (recognition index) and (D) theta or (E) fast gamma power oscillation. *Indicates statistically significant correlation.

Figure 6

Effect of social isolation on the dorsal hippocampus fast gamma and theta oscillations, during social long-term memory retrieval (LTM). (A) Power Spectral Density (PSD) from one representative animal from group-housed (dark lines) and social isolated (grey lines) groups. (B) Theta and (C) fast gamma power during LTM. Correlation between LTM performance (recognition index) and (D) theta or (E) gamma power oscillation. *Indicates statistically significant correlation.

Figure 7

Theta phase/gamma amplitude coupling between the olfactory bulb (OB) and dorsal hippocampus (dHIP) during the retrieval of short (STM) and long-term memory (LTM). Representative theta phase/gamma amplitude coupling between the OB and dHIP during LTM in (A) group-housed and (B) isolated animal. (C) Representative phase-amplitude comodulogram recorded during social exploration. Modulation index during (D) STM and (E) LTM. *Indicate difference between groups. (F) Positive correlation between LTM performance (recognition index) and coupling (modulation index).