Aller au contenuAller au menuAller à la recherche

Séminaire - Carlos Paladini Microcircuitry of the Substantia Nigra Pars Compacta

Abstract :

The dopaminergic neurons of the substantia nigra pars compacta, located within the ventral mesencephalon, encode perhaps one of the most important signals for reinforcement learning in the brain: reward prediction error.  This signal is encoded by the firing pattern of dopaminergic neurons, which controls the release of dopamine at target regions.  

Specifically, transient, impulse-dependent release of dopamine, driven by bursts of action potentials, is critical for natural processing in the brain.  Disruptions of dopamine function result in many of the symptoms of a wide range of psychiatric diseases, drug addiction, and in the extreme case of the degeneration of these cells, to Parkinson's Disease, including many of its cognitive aspects. Identification of the mechanism responsible for bursts is a key step in understanding the mechanism of reinforcement learning, but has so far proven elusive.  
This is largely due to the difficulty in accurately duplicating bursts under controlled experimental conditions such as those attainable during in vitro experiments.  Our lab has developed methods to induce bursts in vitro by manipulating identified afferents and astrocytes.

Selected publications

Cocaine increases dopaminergic neuron and motor activity via midbrain α1 adrenergic signaling.
Goertz RB, Wanat MJ, Gomez JA, Brown ZJ, Phillips PE, Paladini CA.
Neuropsychopharmacology. 2015 Mar 13;40(5):1151-62.

Food restriction increases glutamate receptor-mediated burst firing of dopamine neurons.
Branch SY, Goertz RB, Sharpe AL, Pierce J, Roy S, Ko D, Paladini CA, Beckstead MJ.
J Neurosci. 2013 Aug 21;33(34):13861-72. doi: 10.1523/JNEUROSCI.

Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens. Gaval-Cruz M, Goertz RB, Puttick DJ, Bowles DE, Meyer RC, Hall RA, Ko D, Paladini CA, Weinshenker D.Addict Biol. 2014 Aug 13. doi: 10.1111/adb.12174.

Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior .Zweifel LS, Parker JG, Lobb CJ, Rainwater A, Wall VZ, Fadok JP, Darvas M, Kim MJ, Mizumori SJ, Paladini CA, Phillips PE, Palmiter RD. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7281-8.