Limbic-motor integration by neural excitations and inhibitions in the nucleus accumbens

Abstract

The nucleus accumbens (NAc) has often been described as a "limbic-motor interface," implying that the NAc integrates the value of expected rewards with the motor planning required to obtain them. However, there is little direct evidence that the signaling of individual NAc neurons combines information about predicted reward and behavioral response. We report that cue-evoked neural responses in the NAc form a likely physiological substrate for its limbic-motor integration function. Across task contexts, individual NAc neurons in behaving rats robustly encode the reward-predictive qualities of a cue, as well as the probability of behavioral response to the cue, as coexisting components of the neural signal. In addition, cue-evoked activity encodes spatial and locomotor aspects of the behavioral response, including proximity to a reward-associated target and the latency and speed of approach to the target. Notably, there are important limits to the ability of NAc neurons to integrate motivational information into behavior: in particular, updating of predicted reward value appears to occur on a relatively long timescale, since NAc neurons fail to discriminate between cues with reward associations that change frequently. Overall, these findings suggest that NAc cue-evoked signals, including inhibition of firing (as noted here for the first time), provide a mechanism for linking reward prediction and other motivationally relevant factors, such as spatial proximity, to the probability and vigor of a reward-seeking behavioral response. The nucleus accumbens (NAc) is thought to link expected rewards and action planning, but evidence for this idea remains sparse. We show that, across contexts, both excitatory and inhibitory cue-evoked activity in the NAc jointly encode reward prediction and probability of behavioral responding to the cue, as well as spatial and locomotor properties of the response. Interestingly, although spatial information in the NAc is updated quickly, fine-grained updating of reward value occurs over a longer timescale.

BOLD differences normally attributed to inhibitory control predict symptoms, not task-directed inhibitory control in ADHD

“…Opposite activation of ventral striatum and heightened activation of the amygdala during reward and prediction error processing have consistently been observed in ADHD [11][12][13][14][15][16][17][18]. Heightened amygdala input to the ventral striatum prevents the kind of thresholding influences from ventral to dorsal striatum required for reinforcement learning [19] by enhancing limbic and motor processing while suppressing cognitive processing [20][21][22]. Third, ADHD was characterized by opposite responses in nondopaminergic nuclei (locus coeruleus, raphe and medial septal nuclei) during post-error slowing indicative of a categorically altered competition for control of dopamine [10].…”

Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need

“…In this task, rats perform an approach response to a reward-predictive cue to obtain a highly palatable, calorie-dense liquid food (cream). NAc neurons encode both cued approach and reward consumption phases of such behaviors ( Ambroggi et al, 2011 ; du Hoffmann and Nicola, 2014 ; McGinty et al, 2013 ; Morrison et al, 2017 ; Nicola, 2010 ; Nicola et al, 2004a ; 2004b ; Taha and Fields, 2005 ), and cue-evoked excitations are necessary for the approach response ( Ambroggi et al, 2008 ; du Hoffmann and Nicola, 2014 ; Yun et al, 2004 ). By simultaneously recording from NAc neurons and injecting a MOR antagonist into the NAc, we show that NAc MOR activation is required for both behavioral responding to reward-predictive cues and the neural encoding of those cues by NAc neurons.…”

Disrupted reinforcement learning during post-error slowing in ADHD

“…The hypothalamus is involved in autonomic function, and is a major source of input to dopaminergic projections to the SNS (Menegas et al, 2015). Gating influences from the SNS can be strongly influenced by DA-amygdala interactions, and determine the scope of modular functions that can participate in globally integrated processing at any given time (Fudge and Emiliano, 2003;Haber et al, 2000;Morrison et al, 2017). Altered activities and correlations with the hypothalamus, combined with evidence of limbic-motor interfacing in place of error magnitude related thresholding, would support very different forms of globally integrated processing in ADHD compared to TD…”

“…The lateral connections of the SNS cause the level of activity in more ventral parts of the striatum to affect the threshold for activity in more dorsal parts of the striatum (Haber et al, 2000). Elevated activity in the ventral striatum, such as from heightened amygdala input, therefore causes increased thresholds on the passage of cognitive activities through more dorsal parts of the striatum, referred to as limbic motor interfacing (Mogenson et al, 1980;Morrison et al, 2017). Limbic motor interfacing would thus render the striatum incapable of sustaining error magnitude related thresholding influences in dorsal striatum.…”