Early sensory experiences interact with genes to shape precise neural circuits during development. This process is vital for proper brain function in adulthood. Neurological dysfunctions caused by environmental alterations and/or genetic mutation may share the same molecular or cellular mechanisms. Here, we show that early life bilateral whisker trimming (BWT) subsequently affects social discrimination in adult male mice. Enhanced activation of the hippocampal dorsal CA3 (dCA3) in BWT mice was observed during social preference tests. Optogenetic activation of dCA3 in naive mice impaired social discrimination, whereas chemogenetic silencing of dCA3 rescued social discrimination deficit in BWT mice. Hippocampal oxytocin (OXT) is reduced after whisker trimming. Neonatal intraventricular compensation of OXT relieved dCA3 over-activation and prevented social dysfunction. Neonatal knockdown of OXT receptor in dCA3 mimics the effects of BWT, and cannot be rescued by OXT treatment. Social behavior deficits in a fragile X syndrome mouse model (Fmr1 KO mice) could also be recovered by early life OXT treatment, through negating dCA3 over-activation. Here, a possible avenue to prevent social dysfunction is uncovered.
Sociability is fundamental for our daily life and is compromised in major neuropsychiatric disorders. However, the neuronal circuit mechanisms underlying prosocial behavior are still elusive. Here we identify a causal role of the basal forebrain (BF) in the control of prosocial behavior via inhibitory projections that disinhibit the midbrain ventral tegmental area (VTA) dopamine (DA) neurons. Specifically, BF somatostatin-positive (SST) inhibitory neurons were robustly activated during social interaction. Optogenetic inhibition of these neurons in BF or their axon terminals in the VTA largely abolished social preference. Electrophysiological examinations further revealed that SST neurons predominantly targeted VTA GABA neurons rather than DA neurons. Consistently, optical inhibition of SST neuron axon terminals in the VTA decreased DA release in the nucleus accumbens during social interaction, confirming a disinhibitory action. These data reveal a previously unappreciated function of the BF in prosocial behavior through a disinhibitory circuitry connected to the brain’s reward system.
The development of non-noble metal electrocatalysts with high activity and long-term stability for hydrogen evolution reaction (HER), especially at large current density, is of great significance for industrial hydrogen production...
In addition to cortical areas, the thalamus also displays plasticity during a critical period in early life. Since most sensory information is transmitted to the cortex via the thalamus, it will be of significant interest to understand the precise time window and underlying mechanisms of this critical period in the thalamus. By using in vitro whole-cell patch recording in acute brain slices, we found that VPm relay synapses were only sensitive to whisker deprivation from postnatal day 11 (P11) to P14. Whisker deprivation initiated within the P11 to P14 window significantly reduced the amplitude of AMPAR-EPSCs, but not NMDAR-EPSCs when recorded 24 h after whisker removal. From P10 to P11, the timing for entry into the critical period and the kinetics underlying NMDAR-EPSCs function were significantly altered. At P11, NMDAR-EPSCs were less sensitive to ifenprodil, a selective blocker of NR2B-containing NMDAR, and the protein level of NR2A was significantly increased compared to those at P10. At the end of the critical period there were no obvious changes in synaptic properties when compared between P14 and P15. Using calcium imaging, we found that fewer P15 VPm neurons could be excited by the GABAa receptor agonist, muscimol, when compared to P14 VPm neurons; this correlated to an increase in KCC2 expression. Our studies revealed a precise critical period of sensory experience-dependent plasticity in the thalamus featuring distinct molecular mechanisms which occur at the start and end of this critical window.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.