GABAergic precursor transplantation into the prefrontal cortex prevents phencyclidine-induced cognitive deficits

Daisuke H. Tanaka, Kazuya Toriumi, Ken ichiro Kubo, Toshitaka Nabeshima, Kazunori Nakajima

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Phencyclidine (PCP) is a noncompetitive NMDA receptor antagonist, and it induces schizophreniform cognitive deficits in healthy humans and similar cognitive deficits in rodents. Although the PCP-induced cognitive deficits appear to be accompanied and possibly caused by dysfunction of GABAergic inhibitory interneurons in the prefrontal cortex (PFC), the potential benefit(s) of GABAergic interneuron manipulations on PCP-induced cognitive deficits remains unexplored. In this study we show that when embryonic medial ganglionic eminence(MGE)cells, many of which differentiate into cortical GABAergic interneurons in situ, were grafted into the medial PFC (mPFC) of neonatal mice, they differentiated into a specific class of GABAergic interneurons and became functionally integrated into the host neuronal circuitry in adults. Prior MGE cell transplantation into the mPFC significantly prevented the induction of cognitive and sensory-motor gating deficits by PCP. The preventive effects were not reproduced by either transplantation of cortical projection neuron precursors into the mPFC or transplantation of MGE cells into the occipital cortex. The preventive effects of MGE cell transplantation into the mPFC were accompanied by activation of callosal projection neurons in the mPFC. These findings suggest that increasing GABAergic interneuron precursors in the PFC may contribute to the development of a cell-basedapproach as a novel means of modulating the PFCneuronal circuitryand preventing schizophreniform cognitive deficits.

Original languageEnglish
Pages (from-to)14116-14125
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number40
DOIs
Publication statusPublished - 05-10-2011
Externally publishedYes

Fingerprint

Phencyclidine
Interneurons
Prefrontal Cortex
Median Eminence
Transplantation
Cell Transplantation
Sensory Gating
Neurons
Occipital Lobe
Corpus Callosum
N-Methyl-D-Aspartate Receptors
Rodentia

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Tanaka, Daisuke H. ; Toriumi, Kazuya ; Kubo, Ken ichiro ; Nabeshima, Toshitaka ; Nakajima, Kazunori. / GABAergic precursor transplantation into the prefrontal cortex prevents phencyclidine-induced cognitive deficits. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 40. pp. 14116-14125.
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GABAergic precursor transplantation into the prefrontal cortex prevents phencyclidine-induced cognitive deficits. / Tanaka, Daisuke H.; Toriumi, Kazuya; Kubo, Ken ichiro; Nabeshima, Toshitaka; Nakajima, Kazunori.

In: Journal of Neuroscience, Vol. 31, No. 40, 05.10.2011, p. 14116-14125.

Research output: Contribution to journalArticle

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