Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption

Abstract

The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and population calcium activity from the dorsal striatum during feeding and an operant task that resulted in mice obtaining food pellets. Dorsal striatal neurons exhibited long ramps in activity that preceded actions by several seconds, and may reflect upcoming actions. Understanding how the striatum controls the preparation and generation of actions may lead to improved therapies for disorders, such as drug addiction or obesity.

Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted mice

“…Recently, in freely moving animals, it was reported that both SPN populations become active in localized compact groups of synchronized neurons, that alternate their activity over time (Barbera et al, 2016;Klaus et al, 2017;London et al, 2018), these results are similar to previous slice recordings treated with NMDA . In contrast, slices from DA-depleted animals report neuronal activity locked into a dominant network state with reduced alternations between the assemblies (Jaidar et al, 2010;Lopez-Huerta et al, 2013).…”

Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption

“…Although there were instances where clear changes in input activity were attributed to the DS onset and lever press, particularly in the GCaMP6s recordings, this activity was not consistent across the different recordings of each input ( Figure S3B). These findings are in line with previous research showing that the most widespread and coherent changes in NAc neuron activity tend to coincide with feeding (London et al, 2018;Nicola et al, 2004aNicola et al, , 2004b.…”

“…Electrophysiological recordings in rats performing a similar discriminative stimulus operant task have demonstrated that changes in spiking activity in the NAc are most prevalent and synchronous during food port visits . Also, a recent meta-analysis found that, regardless of the behavioral task, the most prevalent response pattern in the NAc during consumption is a reduction in spiking activity (London et al, 2018). Events preceding consumption, such as operant and approach behavior, are typically associated with sparser and more heterogeneous changes in activity (London et al, 2018;Nicola et al, 2004aNicola et al, , 2004b.…”

Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction

“…To constrain the parameter space for initial recordings, we recorded population Ca 2+ activity of putative dSPNs via fiber photometry, reasoning that all aforementioned possibilities could be read out by neural signals within SPNs of the striatum (Fig.7A-C). In support of this idea, we observed value-related signals leading up to trial initiation (Fig.7D,F; Fig.8A,D,H), consistent with population Ca 2+ imaging signals observed in both SPN subtypes as mice approach palatable food (London et al, 2018). While our imaging does not provide the clarity of cellular-level approaches (Donahue et al, 2019; Kwak and Jung, 2019), it clearly demonstrates two phases of activity – a slow ramp occurring ∼10sec.…”

“…Recent population Ca 2+ imaging of striatal SPN populations has revealed a prolonged ramping activity prior to action sequence initiation (London et al, 2018). Together with our data (Fig.2) and other work documenting the modulation of initiation latency by prior outcome (Bari et al, 2019), we investigated the preinitiation window as one key timeframe for reward-related signals in dorsal striatal direct pathway neurons.…”