The Saddoris Lab

 The Saddoris La
b is primarily focused on understanding the neuroscience of learning and goal-directed behavior. Because the world is a highly dynamic place, animals are tasked with finding stimuli in their environments that will adaptively allow them to obtain rewarding outcomes (such as food or mates) while avoiding dangerous situations (such as predators). A set of neural structures known as the limbic system, which includes the prefrontal cortex, amygdala and nucleus accumbens, form a highly interconnected circuit of structures that coordinate activity to support adaptive learning. In the Saddoris Lab, we employ a combination of techniques in order to understand how these circuits function, including extracellular electrophysiology to record patterns of cellular activity during behavior), electrochemistry (i.e., fast-scan cyclic voltammetry) to record real-time release of dopamine and other electroactive neurochemicals, and optogenetics to selectively manipulate select populations of neurons during discrete phases of learning. By using these techniques in combination with a variety of behaviors, we are working to understand how circuits of neural structures allow new information to be learned and altered through experience.

    Sometimes learning can become pathological, as in the case of drug abuse. While substance use is often undertaken due to the rewarding properties of the drug, the transition to abuse and addiction is marked by preoccupation with drug seeking, decreased interest in previously rewarding activities, and a loss of control over relapsing to drug taking after periods of abstinence. Drug addiction is a serious mental disorder which has profound costs to both the addicted person, as well as their family and society as a whole. To address this, the Saddoris Lab is committed to understanding the ways in which chronic exposure to drugs of abuse alter the neural circuitry of the brain, particularly to the mesolimbic structures that are typically recruited by normal learning pathways. It is our hope that by discovering which circuits are damaged by drugs of abuse and how they are have been altered, we can begin to develop specific targets for potential therapeutics which could contribute to increased success towards drug abstinence.

Commentary on our work:

Commentary in the Journal Club by K.M. Fraser & J.M. Haight (2016). Diminished dopamine: Timing, neuroanatomy, or drug history? Journal of Neuroscience, 36(18), 4907-9.

This Week in The Journal commentary by T. Esch (2015). Dopamine release patterns differ in accumbal core and shell Journal of Neuroscience, 35(33), i.

Commentary by B.T Saunders & P.H. Janak (2014). Nucleus accumbens plasticity underlies multifaceted behavioral changes associated with addiction, Biological Psychiatry, 75, 92-3.

Commentary by Smith, K.S. (2011). Neuronal correlates of normal and drug-potentiated Pavlovian-instrumental transfer [Commentary on Saddoris et al.], European Journal of Neuroscience, 33, 2273-4

Recent Publications:

Saddoris, M.P., Sugam, J.A. & Carelli, R.M. (In press). Prior cocaine experience impairs normal phasic dopamine signals of reward value in accumbens shell. Neuropsychopharmacology.

Dolzani, S.D., Baratta, M.V., Amat, J., Agster, K.L., Saddoris, M.P., Watkins, L., & Maier, S.F. (in press). Activation of habenulo-raphe circuit is critical for the behavioral and neurochemical consequences of uncontrollable stress. eNeuro.

Saddoris, M.P., Wang, X., Sugam, J.A. & Carelli, R.M. (2016). Cocaine self-adminstration experience induces pathological phasic accumbens dopamine signals and abnormal incentive behaviors in drug-abstinent rats. Journal of Neuroscience, 36(1): 235-250.

Saddoris, M.P., Cacciapaglia, F., Wightman, R.M., & Carelli, R.M. (2015). Differential dopamine release dynamics in nucleus accumbens core and shell reveals distinct signals for error prediction and incentive motivation. Journal of Neuroscience, 35(33), 11572-82.
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Saddoris, M.P.*, Sugam, J.A.*, Stuber, G.D., Witten, I.B., Deisseroth, K. & Carelli, R.M. (2015). Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making. Biological Psychiatry, 77(10), 903-15.

Saddoris, M.P., & Carelli, R.M. (2014). Cocaine self-administration abolishes associative neural encoding in the nucleus accumbens necessary for higher-order learning. Biological Psychiatry, 75, 156-64.

Cerri, D.H*, Saddoris, M.P.* & Carelli, R.M. (2014). Nucleus accumbens core neurons encode value-neutral associations but not inferred value during a sensory preconditioning task. Behavioral Neuroscience, 128(5):567-78.

Sugam, J.A.*, Saddoris, M.P.* and Carelli, R.M. (2014). Nucleus accumbens neurons track behavioral preferences and reward outcomes during risky decision making. Biological Psychiatry, 75(10), 807-16.

West, E.A., Saddoris, M.P., Kerfoot, E.C. & Carelli, R.M. (2014). Differential activation of prelimbic versus infralimbic prefrontal cortical activity before and following extended abstinence. European Journal of Neuroscience, 39(11), 1891-1902.

Saddoris, M.P., Sugam, J.A., Cacciapaglia, F. & Carelli, R.M. (2013). Rapid dopamine dynamics in the accumbens core and shell: Learning and action. Frontiers in Bioscience (Elite Ed.), 5, 273-88.

Cacciapaglia, F., Saddoris, M.P., Wightman, R.M, & Carelli, R.M. (2012). Differential dopamine release dynamics in the nucleus accumbens core and shell track distinct aspects of goal-directed behavior for sucrose. Neuropharmacology, 62, 2050-6.

Saddoris, M.P., Stamatakis, A., & Carelli, R.M. (2011). Neural correlates of Pavlovian-to-Instrumental transfer in the nucleus accumbens shell are selectively potentiated following cocaine self-administration. European Journal of Neuroscience, 33, 2274-87.