Biology subjects

Smedley, E. B.

Publications and source records attributed to Smedley, E. B..

4 recordsLinked to original sources

bioRxiv2022

Nucleus accumbens acetylcholine receptors modulate the balance of flexible and inflexible cue-directed motivation

Sign-tracking is a conditioned response where animals interact with reward-predictive cues and can be used as a means to approximate a cues motivational value. The nucleus accumbens core (NAc) has been highly implicated in mediating the sign-tracking response. Additionally, acetylcholine (ACh) transmission throughout the striatum broadly has been attributed to both incentive motivation and behavioral flexibility. Here, we show that sign-tracking responses are indeed flexible in the face of a contingency change in the form of an omission schedule, and that this flexibility is mediated by NAc ACh. Using behavioral and pharmacological methods, we show that blockade of NAc nicotinic receptors (nAChRs) augmented sign-tracking persistence, while blockade of muscarinic receptors (mAChRs) enhanced response flexibility following introduction of the omission schedule. Further, we detail how mAChR or nAChR antagonism impacted the microstructure of sign-tracking responses. These results indicate that NAc ACh receptors have opposing roles in the regulation of sign-tracking response flexibility without altering the motivational value of the cue.

neuroscience↗

bioRxiv2020

Chronic Chemogenetic Manipulation of Ventral Pallidum Targeted Neurons in Rats Fed an Obesogenic Diet.

Current treatments for obesity are unable to reliably reduce weight over time and alternative treatments need to address this challenge. New interventions that target the nervous system could manipulate brain networks underlying reward, metabolic rate and behavior. Here, the ventral pallidum was evaluated as a target of manipulation due to its established role in the networks underlying motivation, pleasure and behavioral output. Chronic inhibitory or excitatory chemogenetic activation was used to modulate the activity of ventral pallidum (VP) targeted neurons in rats on an obesogenic diet. We hypothesized that inhibition of VP activity would decrease the salience of the rats high-sugar, high-fat diet and lead to reduced food consumption and weight gain over time. Paradoxically, measurements of weight, water and food consumption revealed significantly increased weight gain in both groups receiving VP targeted manipulation that was not readily explained by food or water consumption. We theorize that the complex reciprocal feedback between ventral striatal structures (e.g., VP) and metabolic centers of the hypothalamus and brainstem, demonstrated by prior research, likely underpin our findings. This study suggests that the treatment of appetitive disorders (e.g., obesity) with chronic neuromodulation-based interventions could be burdened by the delayed onset of outcomes that are difficult to predict from related prior studies that used acute interventions.

neuroscience↗

bioRxiv2018

Explorations with conditioned stimuli in autoshaping procedures

Sign-tracking is a form of autoshaping where by animals reliably develop conditioned responses toward stimuli that predict an outcome. While the assignment of some value to a predictive cue may be adaptive (i.e., to be alerted to food and water sources), the attribution of value to predictive cues can be maladaptive as seen in behaviors elicited during addiction. Here we test if responding to the predictive cue changes in the context of other cues that are only partially predictive (Experiment 1). Previous work on sequential cues leading to reward have shown a bias in responding toward the first cue in the sequence over learning (Smedley and Smith 2018a, 2018b). Here we test if this effect is unique to discrete cues or if a bias in responding can be seen in a single, long cue (Experiment 2). Finally, we investigate if sign-tracking responses can reliably develop towards a cue that arrives after the delivery of reward (backwards conditioning, Experiment 3). Together, we aim to address various gaps in knowledge about the nature of the sign-tracking response.

animal behavior and cognition↗

bioRxiv2018

Circuit directionality for motivation: lateral accumbens-pallidum, but not pallidum-accumbens, connections regulate motivational attraction to reward cues

Sign-tracking behavior, in which animals interact with a cue that predicts reward, provides an example of how incentive salience can be attributed to cues and elicit motivation. The nucleus accumbens (NAc) and ventral pallidum (VP) are two regions involved in cue-driven motivation. The VP, and subregions of the NAc including the medial shell and core, are critical for sign-tracking, and connections between the medial shell and VP are known to participate in sign-tracking and other motivated behaviors. The NAc lateral shell (NAcLSh) is a distinct and understudied subdivision of the NAc, and its contribution to the process by which reward cues acquire value remains unclear. The NAcLSh has been implicated in reward-directed behavior, and has reciprocal connections with the VP, suggesting that NAcLSh and VP interactions could be important mechanisms for incentive salience. Here, we use DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and an intersectional viral delivery strategy to produce a biased inhibition of NAcLSh neurons projecting to the VP, and vice versa. We find that disruption of connections from NAcLSh to VP reduces sign-tracking behavior while not affecting consumption of food rewards. In contrast, VP to NAcLSh disruption affected neither sign-tracking nor reward consumption, but did produce a greater shift in animals behavior more towards the reward source when it was available. These findings indicate that the NAcLSh[->]VP pathway plays an important role in guiding animals towards reward cues, while VP[->]NAcLSh back-projections may not and may instead bias motivated behavior towards rewards.

neuroscience↗