Periodic Reporting for period 3 - SocialNAc (Circuit and synaptic plasticity mechanisms of approach and avoidance social behavior.)
Reporting period: 2023-06-01 to 2024-11-30
In this grant proposal, we ask how the brain encodes the valence of social interaction. We focused on the nucleus accumbens (NAc), a brain region implicated in social reward processing. We described different types of valence-dependent synaptic plasticity at the insular cortex to Nucleus accumbens synapses which teach the animal to approach or avoid a conspecific in the future. The objectives will be to investigate the synaptic mechanisms underlying the approach and avoidance of social behavior at these synapses and to identify the contribution of other inputs to the nucleus accumbens in social interaction.We are investigating the amygdala and the prefrontal cortex inputs to the NAc.
In aim 2, we proposed investigating how neuronal activity in the NAc enables the approach and avoidance of social behavior. We recorded the calcium activity of medium spiny neurons containing D1 receptors using a miniscope and observed that they are activated during social interactions regardless of valence. We then employed a neural activity-dependent labeling approach to investigate which inputs promote D1-MSN activity during prosocial and aversive experiences. We identified neurons activated by prosocial and aggressive experiences in the Anterior Insular Cortex (AIC). We observed that afferent D1-expressing neurons of the anterior insular cortex (AIC) exhibited distinct activity patterns coding for prosocial and aggressive social interaction, respectively. According to a machine learning data analysis approach, calcium activity in D1-AIC neurons projecting to LNAc can be used to decode the valence of social contact.
In aim 1, we proposed investigating the synaptic mechanism underlying social avoidance and approach behavior. We, therefore, focused on AIC to NAc inputs, and using behavioural analysis and patch clamp techniques, we found that distinct forms of synaptic plasticity were elicited at the AIC to NAc synapses in the function of social valence. We concluded that the valence of social interaction induces distinct neural activity in the AIC, which teaches the animal to approach and avoid conspecifics in the future.
We have performed mini scopes recordings from the Nucleus Accumbens and the Interior Insular Cortex, and we have performed AI-driven data analysis. We have related the activity of AIC to NAc pathways with specific forms of synaptic plasticity and performed optogenetic experiments to prove the causality between plasticity and behavior.
In aim 3 In this context we have deconstruct the contribution of sensoy cues in social approach using a three chambered interaction task. Our results highlight and provide proof for the importance of olfactory cues in approach behavior. Subsequently, using in vivo recordings in freely moving mice we interrogated whether a social odor would activate DA neurons of the VTA in the same way as a juvenile conspecific would. In fact, our data demonstrate that complex social stimuli and decomposed social odor cues result in different activation patterns of VTA DA neurons. Moreover, using a four‐choice task, we further show that mice prefer to explore complex social stimuli compared to isolated sensory cues.
we planned to investigate which social-related information is conveyed to the NAc. Preliminary data concerning this aim suggest that projections from the amygdala to the NAc convey information regarding social odor recognition. We are currently investigating the amygdala and the prefrontal cortex inputs to the NAc.
In aim 1, we proposed investigating the synaptic mechanism underlying social avoidance and approach behavior. We, therefore, focused on AIC to NAc inputs, and using behavioural analysis and patch clamp techniques, we found that distinct forms of synaptic plasticity were elicited at the AIC to NAc synapses in the function of social valence. We concluded that the valence of social interaction induces distinct neural activity in the AIC, which teaches the animal to approach and avoid conspecifics in the future.
We have performed mini scopes recordings from the Nucleus Accumbens and the Interior Insular Cortex, and we have performed AI-driven data analysis. We have related the activity of AIC to NAc pathways with specific forms of synaptic plasticity and performed optogenetic experiments to prove the causality between plasticity and behavior.
In aim 3 In this context we have deconstruct the contribution of sensoy cues in social approach using a three chambered interaction task. Our results highlight and provide proof for the importance of olfactory cues in approach behavior. Subsequently, using in vivo recordings in freely moving mice we interrogated whether a social odor would activate DA neurons of the VTA in the same way as a juvenile conspecific would. In fact, our data demonstrate that complex social stimuli and decomposed social odor cues result in different activation patterns of VTA DA neurons. Moreover, using a four‐choice task, we further show that mice prefer to explore complex social stimuli compared to isolated sensory cues.
we planned to investigate which social-related information is conveyed to the NAc. Preliminary data concerning this aim suggest that projections from the amygdala to the NAc convey information regarding social odor recognition. We are currently investigating the amygdala and the prefrontal cortex inputs to the NAc.
a first manuscript has been published in European Journal of Neuroscience (Deconstructing the contribution of sensory cues in social approach) while a second one have been submitted and published as pre print in BiorXiv