University of Illinois at Chicago

Signals of Physiological Status Modulate Food- and Food Cue-Driven Activity of Dopamine Neurons

Download (3.32 MB)
posted on 2023-05-01, 00:00 authored by Vaibhav Ramanath Konanur
An animal’s survival depends on a stable internal physiological status. Homeostasis must be maintained to adaptively navigate the world. Various physiological mechanisms are controlled within narrow ranges and deviations from homeostasis are detrimental to the organism’s survival. Return to homeostasis is critical and largely governed by the organism’s adaptive motivated behaviors. One neural substrate that initiates and maintains motivated behaviors is the mesolimbic dopamine system. Food and food associated stimuli evoke phasic increases in dopamine neuronal activity and dopamine release that correlate with approach behavior. Moreover, physiological state changes how food and food-cues influence behaviors that are dependent on phasic dopamine signaling. However, it is unclear how physiological state modulates dopamine signaling to generate appropriate behaviors. Identifying modulators of dopamine response magnitude may serve as viable interventions for maladaptive motivated behavior. The present thesis aims to explore signals that convey physiological state information to the mesolimbic dopamine system in the service of motivated behaviors and ultimately, homeostasis. Within homeostasis, energy status is tightly controlled. Perturbations in available energy generate hunger or satiety, leading an organism to engage in or cease behaviors directed at calories, respectively. Manipulating physiological state and understanding its role in modulating dopamine signaling will help unravel the neural circuitry of motivated behaviors. The central nervous system to conveys energy status through many signals, including glucose and glucagon-like peptide 1 (GLP-1). Glucose is a ubiquitous energy substrate monitored by the brain. Importantly, low glucose utilization (cytoglucopenia) is detected by the brain to promote robust motivated behavior directed at food - and is refered as a 'hunger’ signal. Conversely, GLP-1 acts to suppress food intake and is known as a ‘satiety’ signal. Here, I manipulated these signals while measuring mesolimbic dopamine neural activity to characterize a node in a circuit responsive to appetitive and consummatory food reward. My research elucidates the neural mechanisms, originating in the mesolimbic dopamine system, that process food and food-cues in the face of caloric deficit and surfeit. In the first study I recorded real-time dopamine neuron activity in the ventral tegmental area (VTA) using a calcium sensor, GCaMP, while subjects were given intraoral sucrose. Central cytoglucopenia increased the magnitude of phasic VTA dopamine signaling evoked by intraoral sucrose and by sucrose associated cues. Interestingly, cytoglucopenia failed to augment water evoked phasic dopamine signaling, supporting that this circuit is tuned toward caloric stimuli. Furthermore, forebrain cytoglucopenia but not hindbrain cytoglucopenia potentiated sucrose-cue evoked phasic VTA dopamine signaling, suggesting a forebrain control of learned associations. In contrast, only hindbrain cytoglucopenia potentiated sucrose evoked VTA dopamine signaling, implying that hindbrain circuits may provide the VTA information regarding the sucrose reward. In the second study, I recorded activity in dopamine neurons with GCaMP while subjects were allowed to approach and ingest sucrose from a sipper which was preceded by an audio cue. I showed that GLP-1 suppressed phasic dopamine signaling to sucrose and sucrose-associated cues, while also suppressing food-directed behaviors. Together, this work supports that cytoglucopenia and GLP-1R signaling modulate eating behavior via central dopamine signaling.



Roitman, Mitchell F


Peters, Christian J



Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Roitman, Jamie D McGehee, Daniel Richmond, Janet

Submitted date

May 2023

Thesis type



  • en

Usage metrics


    No categories selected


    Ref. manager