Home Investigators Howard L. Fields, M.D., Ph.D. Fields Lab Members Saleem M. Nicola
Saleem M. Nicola PDF Print E-mail
snicola.jpgAssistant Professor, Department of Psychiatry and Behavioral Sciences

Contact Information:
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 111
Bronx, NY 10461
Tel: (718) 430-2667
Email: This e-mail address is being protected from spambots, you need JavaScript enabled to view it


Research: A Neural Circuit Underlying Dopamine-Mediated Behavior Selection

Human and animal behavior is guided by cues. The brain constantly evaluates new sensory information and adjusts behavior to maximize reward and minimize aversive consequences. Understanding how the brain decides to change behavior based on cues is thus profoundly important for understanding brain function, not least because such an understanding could facilitate the development of treatments for diseases in which cue-elicited behavior selection is aberrant. Drug addiction is such a disease: in response to stimuli that predict drug availability, addicts pursue drug despite grave consequences for themselves and their families. Even addicts who have remained drug-free for months or years are susceptible to relapse in the presence of drug-predictive cues. One common feature of all drugs of abuse is that they cause an increase in the release of dopamine in the nucleus accumbens, the ventral-most portion of the striatum. To better understand how accumbens dopamine contributes to behavior selection in response to cues, we conducted a series of behavioral, pharmacological and electrophysiological studies.

We trained animals to perform a simple task in which they were required to perform an operant response to a cue in order to obtain a sucrose reward. Microinjection of either D1 or D2 dopamine receptor antagonists into the accumbens severely impaired the ability of animals to respond to cues, while having little effect on tasks that did not require cue responding. Thus, both D1 and D2 receptor activation is specifically required to respond to reward-predictive cues. To investigate the mechanism of this effect of dopamine in the accumbens, we recorded the spiking activity of neurons in the accumbens while animals performed a cue-responding task. Subpopulations of neurons were excited or inhibited by presentation of predictive cues. These cue-evoked neuronal responses were abolished by transient inactivation of the ventral tegmental area, the midbrain nucleus containing dopamine neurons that project to the accumbens. Coupled with the finding that dopamine antagonists injected into the accumbens reduce behavioral responding to cues, these results indicate that cue-evoked accumbens firing patterns are dopamine-dependent and drive the behavioral response to cues.

In further behavioral studies, we found that transient inactivation of the accumbens with tetrodotoxin or glutamate receptor antagonists had effects dissimilar to those of dopamine antagonist injection. Instead of reducing cue responsivity, accumbens inactivation increased responding to non-reward predictive cues. These results are consistent with the idea that accumbens neurons both dopamine-dependently promote specific responses to cues and dopamine-independently inhibit responding, perhaps because accumbens neurons influence behavior through direct (activating behavior) and indirect (inhibiting behavior) output pathways.


Recent Publications:

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.

Nicola SM (2007) The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology 191:521-550.

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, Hopf FW and Hjelmstad GO (2004) Contrast enhancement: a physiological effect of striatal dopamine? Cell Tissue Res. 318:93-106.

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. 154:19-30.

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.

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.

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.

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, 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 Malenka RC (1998) Modulation of synaptic transmission by dopamine and norepinephrine in ventral but not dorsal striatum. J. Neurophysiol. 79:1768-1776.

Nicola SM (1997) Modulation of synaptic transmission by psychostimulants and dopamine in the nucleus accumbens. PhD thesis, University of California, San Francisco.

Nicola SM and Malenka RC (1997) Dopamine depresses excitatory and inhibitory synaptic transmission by distinct mechanisms in the nucleus accumbens. J. Neurosci. 17:5697-5710.

Nicola SM, Kombian SB and Malenka RC (1996) Psychostimulants depress excitatory synaptic transmission in the nucleus accumbens via presynaptic D1-like dopamine receptors. J. Neurosci. 16:1591-1604.

Cummings JA, Nicola SM and Malenka RC (1994) Induction in the rat hippocampus of long-term potentiation (LTP) and long-term depresssion (LTD) in the presence of a nitric oxide synthase inhibitor. Neurosci. Lett. 176:110-114.