Recent work has shown that, as voluntary actions are learned and repeated, there is a shift in behavioral control from a goal-directed and attentional mode to a more habitual and automatic mode. This process is known as habit formation and involves a shift in the cortico-basal ganglia neural circuits controlling behavior. Although the basic neural circuits underlying habit formation have been identified, there remain significant gaps in our understanding. In particular, the conditions promoting habit formation are not yet fully understood, making it difficult to understand the underlying neural mechanisms. The present proposal will elucidate the mechanisms underlying habit formation as well as long-term maintenance. The long-term goal is to understand how different feedback patterns can alter neural signaling in the cortico-basal ganglia network and promote the formation and maintenance of habits. The central hypothesis is that the pattern of self-generated feedback is a critical determinant of habit formation. In particular, different feedback patterns result in different patterns of dopaminergic signaling with distinct consequences on synaptic plasticity and transmission in specific basal ganglia pathways. Using instrumental conditioning in a mouse model, the proposed experiments will examine sensitivity to changes in motivational state and persistence in the face of changes in feedback functions. The chief innovative feature of this proposal is that it combines for the first time quantitative behavioral analysis with in vivo multi-electrode and ex vivo whole-cell patch-clamp electrophysiological techniques in genetically modified animals. The proposed experiments will also examine mechanisms underlying habit formation at multiple levels of analysis. The proposed research is significant because it will shed light on the cellular, molecular, and circuit mechanisms for the transition to habitual control and behavioral automaticity in spite of environmental disturbance. Results from the proposed experiments can have significant implications for the development of novel strategies to promote behavioral patterns contributing to healthy lifestyles.
The proposed research is relevant to public health because the discovery of the mechanisms of habit formation is critical for the development of novel strategies for preventing undesirable habits, such as those associated with addiction, and promoting desirable habits, such as those promoting a healthy lifestyle. It is relevant to the part of NIH's mission that pertains to developing knowledge to reduce the burdens of human disability.
|Rossi, Mark A; Li, Haofang E; Lu, Dongye et al. (2016) A GABAergic nigrotectal pathway for coordination of drinking behavior. Nat Neurosci 19:742-748|
|O'Hare, Justin K; Ade, Kristen K; Sukharnikova, Tatyana et al. (2016) Pathway-Specific Striatal Substrates for Habitual Behavior. Neuron 89:472-9|
|Wang, Xiaoming; Bey, Alexandra L; Katz, Brittany M et al. (2016) Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism. Nat Commun 7:11459|
|Kim, Il Hwan; Rossi, Mark A; Aryal, Dipendra K et al. (2015) Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. Nat Neurosci 18:883-91|
|Rossi, Mark A; Calakos, Nicole; Yin, Henry H (2015) Spotlight on movement disorders: What optogenetics has to offer. Mov Disord 30:624-31|
|Leblond, Mona; Sukharnikova, Tatyana; Yu, Chunxiu et al. (2014) The role of pedunculopontine nucleus in choice behavior under risk. Eur J Neurosci 39:1664-70|
|Yin, Henry H (2014) Action, time and the basal ganglia. Philos Trans R Soc Lond B Biol Sci 369:20120473|
|Rossi, Mark A; Sukharnikova, Tatyana; Hayrapetyan, Volodya Y et al. (2013) Operant self-stimulation of dopamine neurons in the substantia nigra. PLoS One 8:e65799|
|Rossi, Mark A; Fan, David; Barter, Joseph W et al. (2013) Bidirectional modulation of substantia nigra activity by motivational state. PLoS One 8:e71598|