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Neuron. 2018 Aug 8;99(3):540-554.e4. doi: 10.1016/j.neuron.2018.06.044. Epub 2018 Jul 26.

Dopamine Triggers the Maturation of Striatal Spiny Projection Neuron Excitability during a Critical Period.

Author information

1
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
2
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Movement Disorders, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
3
Division of Movement Disorders, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
4
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Movement Disorders, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: ds43@cumc.columbia.edu.

Abstract

Neural circuits are formed and refined during childhood, including via critical changes in neuronal excitability. Here, we investigated the ontogeny of striatal intrinsic excitability. We found that dopamine neurotransmission increases from the first to the third postnatal week in mice and precedes the reduction in spiny projection neuron (SPN) intrinsic excitability during the fourth postnatal week. In mice developmentally deficient for striatal dopamine, direct pathway D1-SPNs failed to undergo maturation of excitability past P18 and maintained hyperexcitability into adulthood. We found that the absence of D1-SPN maturation was due to altered phosphatidylinositol 4,5-biphosphate dynamics and a consequent lack of normal ontogenetic increases in Kir2 currents. Dopamine replacement corrected these deficits in SPN excitability when provided from birth or during a specific period of juvenile development (P18-P28), but not during adulthood. These results identify a sensitive period of dopamine-dependent striatal maturation, with implications for the pathophysiology and treatment of neurodevelopmental disorders.

KEYWORDS:

Kir2; PIP2; adolescence; critical period; development; dopamine; intrinsic excitability; spiny projection neuron; striatum

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