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. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Curr Behav Neurosci Rep. 2015 Jul 12;2(3):146–153. doi: 10.1007/s40473-015-0044-3

Figure 1.

Figure 1

(a) This simplified schematic depicts the major glutamatergic afferents (red) to nucleus accumbens (NAc) medium spiny neurons. The VTA sends dopaminergic projections to NAc (green) as well as PFC and HIP (light green). Interneurons and NAc medium spiny neurons provide GABAergic input (blue). The lateral hypothalamus, lateral habenula, dorsal striatum, and ventral pallidum have been omitted for clarity, though they also play important roles in the reward circuit. VTA (ventral tegmental area) AMY (amygdala) PFC (prefrontal cortex) HIP (hippocampus) ILT (intralaminar thalamus)

(b) Optogenetic stimulation of glutamatergic thalamostriatal synapses increased social avoidance behavior in a recent study by Christoffel and Golden, et al [42]. After chronic social defeat stress, susceptible mice displayed baseline increases in the strength of thalamic synapses in the ventral striatum, as measured by increased vesicular glutamate transporter-2 protein and increased AMPA to NMDA receptor ratio on medium spiny neurons with optogenetic stimulation of thalamic terminals.

(c) The basolateral amygdala (BLA) projection to NAc signaled positive reward reinforcement and stimulation of this projection promoted intracranial self-stimulation (ICSS) in a recent study by Namburi, et al [70]. The study expanded upon earlier work showing the rewarding effects of BLA to NAc terminal stimulation [47]. After sucrose reward conditioning, BLA neurons that project to the NAc displayed increased synaptic strength as measured by increased AMPA to NMDA ratio. In an ICSS task, animals increasingly nose-poked for optogenetic stimulation of BLA neurons that project to the NAc.

(d) VTA dopamine neuron firing and Ih current was previously shown to increase in susceptible animals after chronic social defeat stress [14]. A recent study demonstrated that resilient mice have even larger Ih currents along with increased potassium (K+) channel currents [77]. Enhancing this resiliency mechanism by stimulating dopamine cells or by increasing potassium channel currents promoted increased social interaction.