Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making

Abstract

SUMMARY Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, ’rational’ decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond to increased activity of their striosome-predominant striatal projection neuron targets and to decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked, or be mimicked, by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict.

Compartmental function and modulation of the striatum

“…First, although some overlap certainly exists, afferents are often categorically segregated: in the dorsal striatum, limbic-associated cortical and subcortical regions (including portions of the prelimbic, orbitofrontal and anterior insular cortices and basolateral nuclei of the amygdala) preferentially innervate striosomes, whereas projections from somatosensory and motor cortices preferentially innervate the matrix. Consistent with this, recent studies utilizing viral tracing techniques that functionally and visually label corticostriatal axonal fields detect preferential connectivity between the prelimbic cortex and striosomes and anterior cingulate cortex and matrix (Friedman et al, 2015(Friedman et al, , 2017. Despite the wealth of evidence for compartmental segregation of striatal afferents, recent work employing new methodologies has called much of this into question (we refer the reader to Brimblecombe and Cragg (2017) and Gerfen, Paletzki, and Heintz (2013) for further information about new mouse lines used to isolate and interrogate compartments and their afferents/efferents).…”

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

“…Cost-benefit decision-making is derived from the paradigm described above, but instead of a physical effort, animals rank options in order to receive a higher reinforcement. For example, the animal is exposed to i-a high cost-high benefit choice: between pure chocolate reward paired with the presence of an aversive strong light or ii-a low cost-low benefit choice: between diluted chocolate milk paired with dim light (Friedman et al, 2017). In risk-based decision-making the animal has to choose between two chambers, each associated with different reinforcement delivery rates.…”

Microstimulation of primate neocortex targeting striosomes induces negative decision‐making

“…However, there is no evidence definitively identifying a corticostriatal circuit related to such challenging decision‐making, known in humans to be deleteriously affected in neuropsychiatric disorders including anxiety and depression (Pizzagalli, ). The presumed rodent homologue of the pACC has been implicated in circuits related to the striosome compartment of the striatum (Banghart, Neufeld, Wong, & Sabatini, ; Friedman et al., , ; Yoshizawa, Ito, & Doya, ), a highly distinct set of labyrinthine zones (“striosomes”) distinguished from the surrounding matrix by their neurochemical composition (Graybiel, ; Graybiel & Ragsdale, ) and connections with the limbic system (Brimblecombe & Cragg, ; Fujiyama et al., ). Potential homologies between rodent and primate, however, have been questioned, especially for medial prefrontal corticostriatal circuits (Heilbronner, Rodriguez‐Romaguera, Quirk, Groenewegen, & Haber, ).…”