Natural Neural Projection Dynamics Underlying Social Behavior

Abstract

Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics.

Dopaminergic Dynamics Contributing to Social Behavior

“…) behavior, but instead drove aversion and anxiety-related behaviors (Gunaydin et al 2014). Accordingly, there is no current evidence that VTA projections play a causal role within the PFC in modulating the PFC's important role in social behavior regulation, although certainly this mesocortical circuit could provide subthreshold modulation of the relevant circuitry or other glutamatergic cortical inputs, whereas under these conditions, activation alone is not sufficient to alter social behavior.…”

“…We are grateful to our coauthors on Gunaydin et al (2014), from which the figures and related text were adapted, as well as to the sources of support described therein (including the National Institutes of Health, the Defense Advanced Research Projects Agency, the Simons Foundation, and the Gatsby Foundation), and to all of the members of the Deisseroth lab.…”

“…However, a circuit-level understanding of which DA cells, projections, and postsynaptic targets mediate these effects and how they interact in real time during behavior has remained largely unknown. This problem was recently addressed using all-optical readout and control of DA neurons in socializing mice to understand how genetically specified cells and projections are causally involved in driving social behavior (Gunaydin et al 2014). …”

“…To observe socially relevant native patterns of neural activity in real time, the genetically encoded Ca 2þ indicator GCaMP5, which changes its fluorescence properties upon elevation of Ca 2þ levels inside the cell (a wellestablished proxy for neural activity), was used to record temporally precise Ca 2þ transients (Akerboom et al 2012;Chen et al 2013) in VTA DA neurons (Gunaydin et al 2014). To selectively target dopaminergic neurons in the VTA, a virus carrying Cre-dependent GCaMP5 was injected into the VTA of mice expressing Cre recombinase under the tyrosine hydroxylase (TH) promoter (TH::Cre mice).…”

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

“…The use of optically active rhodopsin chimeric receptors, however, has allowed us to manipulate neurocircuitry in vivo, with higher specificity to endogenous mechanisms (Airan et al, 2009). Currently, there are several chimeric receptors that upon photoactivation are able to signal intracellularly via G-protein-and arrestin-mediated cascades: α 1 -adrenergic, β 2 -adrenergic, adenosine A 2A , 5HT1A, μ-opioid receptor, and the D1 dopamine receptor (Airan et al, 2009;Bailes et al, 2012;Barish et al, 2013;Franke et al, 1992;Gunaydin et al, 2014;Kim et al, 2005;Li et al, 2015;Oh et al, 2010;Siuda et al, 2015a, b). Here we incorporate the chimeric rhodopsin/β 2 -adrenergic receptor (opto-β 2 AR) and show that activation of CaMKIIα+ neurons in the BLA via simulated β-adrenergic activation induces both acute and social anxiety-like states.…”