HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 586/8/2143    most recent jphysiol.2007.148965v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Blomeley, C. Articles by Bracci, E. PubMed PubMed Citation Articles by Blomeley, C. Articles by Bracci, E. Related Collections Neuroscience

¹ Faculty of Life Sciences, University of Manchester, Manchester M60 1QD, UK

The striatum is the main basal ganglia input nucleus, receiving extensive glutamatergic inputs from cortex and thalamus. Medium spiny striatal projection neurons (MSNs) are GABAergic, and their axon collaterals synapse on other MSNs. Approximately 50% of MSNs corelease substance P (SP), but how this neurotransmitter controls MSN activity is poorly understood. We used whole-cell recordings to investigate how SP affects MSNs and their glutamatergic inputs. SP elicited slow depolarizations in 47/90 MSNs, which persisted in the presence of tetrodotoxin (TTX). SP responses were mimicked by the NK1 receptor agonist [Sar9,Met(O₂)11]-substance P (SSP), and fully blocked by the NK1 receptor antagonists L-732,138, or extracellular zinc. When intracellular chloride was altered, the polarity of SP responses depended on the sign of the chloride driving force. In voltage-clamp, SP-induced currents reversed around –68 mV and displayed marked inward rectification. These data indicate that SP increased a ClC-2-type chloride conductance in MSNs, acting through NK1 receptors. SP also strongly increased glutamatergic responses in 49/89 MSNs. Facilitation of glutamatergic responses (which was observed both in MSNs directly affected by SP and in non-affected ones) was reduced by application of L-732,138, and fully blocked by coapplication of L-732,138 and SB222200 (an NK3 receptor antagonists), showing that both NK1 and NK3 receptors were involved. SP-induced facilitation of glutamatergic responses was accompanied by a marked decrease in paired-pulse ratio, indicating a presynaptic mechanism of action. These data provide an electrophysiological correlate for the anatomically known connections between SP-positive MSN terminals and the dendrites and somata of other MSNs.

(Received 29 November 2007; accepted after revision 25 February 2008; first published online 27 February 2008)
Corresponding author E. Bracci: Faculty of Life Sciences, University of Manchester, Manchester M60 1QD, UK. Email: e.bracci{at}manchester.ac.uk