Assistant Professor, Department of Psychiatry and Behavioral Sciences
Assistant Professor, Dominick P. Purpura Department of Neuroscience
Contact: saleem (((dot))) nicola ((((at)))) einstein . yu . edu
My lab focuses on understanding the neural circuits underlying reward-seeking and addictive behaviors. We use a systems-level approach that combines behavioral, pharmacological and electrophysiological techniques in awake, freely moving animals.
We begin by identifying a hypothesis regarding the neural circuits underlying a particular behavior. For example, the nucleus accumbens (part of the ventral striatum) projects to motor output structures of the basal ganglia. The accumbens also receives input from limbic structures that have been suggested to process stimuli that predict events of consequence to the animal's well-being (that is, stimuli that predict reward, such as the sound of water falling heard by a thirsty animal, or aversive events, such as the sound of a predator). These limbic structures include the basolateral amygdala, which sends glutamatergic axons to the accumbens, and the ventral tegmental area (VTA), which sends a dopamine projection. Therefore, we hypothesized that the amygdala and VTA projections to the accumbens are part of the neural circuit that controls the animal's response to reward-predictive stimuli.
To test this hypothesis, we designed a behavioral task that requires rats to respond, by pressing a lever, to an auditory stimulus that predicts sucrose reward. We then determined that the dopamine projection to the accumbens is required for this behavior by demonstrating that dopamine receptor antagonists microinjected directly into the animals' nucleus accumbens caused animals to cease responding to the stimulus. We also showed that transient inactivation of the amygdala had the same effect. Next, we used multiple simultaneous single-unit recordings of neurons in the accumbens and amygdala to demonstrate that subpopulations of neurons were excited or inhibited by the reward-predictive stimulus.
Finally, we established that stimulus-evoked excitations and/or inhibitions in the accumbens are required for the reward-seeking behavior instigated by the stimulus. We did this by inactivating the dopaminergic VTA neurons while recording from accumbens neurons during the stimulus-evoked reward seeking task; this manipulation selectively abolished the firing of accumbens neurons responsive to reward-predictive stimuli. These experiments established that a specific neural circuit (the dopaminergic projection from the VTA to the accumbens) is part of the larger circuit that underlies stimulus-evoked reward-seeking behavior. Ongoing experiments using a similar combination of local microinjections and electrophysiological recording seek to demonstrate that the excitatory amygdala to accumbens projection is also part of this circuit. Other experiments utilize electrophysiological and pharmacological techniques to determine the information encoded by neuronal firing (for instance, does the firing of an accumbens neuron in response to a reward-predictive stimulus direct the motor system to perform a specific reward-seeking task, or does it simply inform downstream nuclei that a reward is available? What specific role does dopamine play in modulating this firing?)
Drugs of abuse can also serve as rewards, often to the extent that drug-seeking (sometimes in response to drug-predictive stimuli) becomes excessive and harmful. A long-term goal of these experiments is to use our increasing knowledge of the neural circuits that control reward-seeking to ask how these circuits produce aberrant behavior (excessive drug-seeking) in addiction.
Nicola SM, Surmeier DJ and Malenka RC (2000) Dopaminergic Modulation of Neuronal Excitability in the Striatum and Nucleus Accumbens. Annu. Rev. Neurosci. 23:185-215.
Nicola SM and Deadwyler SA (2000) Firing Rate of Nucleus Accumbens Neurons is Dopamine-Dependent and Reflects the Timing of Cocaine-Seeking Behavior in Rats on a Progressive Ratio Schedule of Reinforcement J. Neurosci. 20:5526-5537.
Nicola SM, Yun IA, Wakabayashi HL and Fields HL (2004) Cue-evoked firing of nucleus accumbens neurons encodes motivational significance during a discriminative stimulus task. J. Neurophsyiol. 91:1840-1865.
Nicola SM, Yun IA, Wakabayashi HL and Fields HL (2004) Firing of nucleus accumbens neurons during the consummatory phase of a discriminative stimulus task depends on previous reward predictive cues. J. Neurophsyiol. 91:1866-1882.
Yun IA, Wakabayashi KT, Fields HL and Nicola SM (2004) The ventral tegmental area is required for the behavioral and nucleus accumbens neuronal firing responses to incentive cues. J. Neurosci. 24:2923-2933.
Wakabayashi KT, Fields HL and Nicola SM (2004) Dissociation of the role of nucleus accumbens dopamine in responding to reward-predictive cues and waiting for reward. Behav. Brain Res. 54:19-30.
Yun IA, Nicola SM, and Fields HL (2004) Contrasting effects of dopamine and glutamate receptor antagonist injection in the nucleus accumbens suggest a neural mechanism underlying cue-evoked goal-directed behavior. Eur. J. Neurosci. 20:249-263.
Nicola SM, Hopf FW and Hjelmstad GO (2004) Contrast enhancement: a physiological effect of striatal dopamine? Cell Tissue Res. 318:93-106.
Nicola SM, Taha SA, Kim SW and Fields HL (2005) Nucleus accumbens dopamine release is necessary and sufficient to promote the behavioral response to reward-predictive cues. Neuroscience 135:1025-1033.
Nicola SM (2007) The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology 191:521-550.
Fields HL, Hjelmstad GO, Margolis EB and Nicola SM (2007) Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu. Rev. Neurosci. 30:289-316.
Ishikawa A, Ambroggi F, Nicola SM and Fields HL (2008) Dorsomedial prefrontal cortex contribution to behavioral and nucleus accumbens neuronal responses to incentive cues. J. Neurosci. 28:5088-5098.
Ishikawa A, Ambroggi F, Nicola SM and Fields HL (2008) Contributions of the amygdala and the dorsal and ventral medial prefrontal cortex to incentive cue responding. Neuroscience 155:573-584.
Ambroggi F, Ishikawa A, Fields HL and Nicola SM (2008) Incentive cue encoding in the nucleus accumbens depends on basolateral amygdala inputs. Neuron 59:648-661.
Nicola SM (2010) The flexible approach hypothesis: Unification of effort and cue responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior. J. Neurosci. 8:16585-15600.
Ambroggi F, Ghazizadeh A, Nicola SM, Fields HL (2011) Roles of nucleus accumbens core and shell in incentive cue responding and behavioral inhibition. J. Neurosci. 31:6820-6830.
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 111
Bronx, NY 10461