[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 274.9/JJ4
Topic: D.15.a. Transmitters and neuromodulation
Support: NIAAA DISCBR
Title: Effects of D1 and D2 type dopamine receptor blockade on striatal activity and synchrony
Authors: *J. M. BURKHARDT 1,2 , R. M. COSTA 1 ;
1 Natl. Inst. of Alcoholi, Natl. Inst. of Hlth., Bethesda, MD; 2 Physiol. & Pharmacol., Wake Forest
Univ., Winston-Salem, NC
Abstract: In Parkinson's disease (PD) loss of the dopaminergic (DA) neurons in the substantia
nigra pars compacta eventually leads to motor dysfunction and akinesia. We have previously
shown that DA depletion leads to both changes in firing rate and in synchrony in the basal
ganglia. Since D1 and D2 receptors are preferentially expressed in striatonigral and
striatopallidal medium spiny neurons, respectively, we decided to investigate the role of D1 and
D2 receptors in DA control of corticostriatal synchrony and voluntary movement. We
chronically implanted mice with multielectrode arrays in the dorsolateral and dorsomedial
striatum and investigated the effects of blocking both D1 and D2 receptor types, or D1 or D2
alone, on movement, firing rate, and synchrony of striatal medium spiny neurons. Intraperitoneal
administration of a D1 antagonist (SCH-23390, 0.4 mg/kg i.p.) or a D2 antagonist (raclopride,
2.0 mg/kg i.p.) substantially reduced locomotion, and co-administration of D1 and D2
antagonists rendered the mice completely akinetic. In vivo recordings were performed for 30
minutes prior to and 60 minutes subsequent to dopamine receptor blockade or saline
administration. We found that blockade of D1+D2 receptor types changed the firing rate of the
majority of putative medium spiny neurons recorded, with a net decrease on average firing rate.
Blockade of both D1+D2 receptors also caused an increase in crosscorrelated activity and in the
number of neurons with activity entrained to the local field potential (LFP) oscillations.
Blockade D2 receptors alone was sufficient to produce changes in striatal firing rate with a net
decrease in rate after injection, and also a substantial increase in synchrony. However, D1
blockade seemed to affect rate differently than D2. Although the majority of neurons changed
firing rate after D1 blockade, the net population vector did not change. Also, the effects of D1
blockade on synchrony seemed less pronounced than the effects of D2 blockade, and D1+D2
blockade. Taken together, these results suggest that both D1 and D2 receptors contribute to the
changes observed in basal ganglia circuits after dopamine depletion, but D2 receptors seem to
have a more prominent role in decreasing average firing rate and increasing synchrony. Because
D2 receptors are expressed in different cell types in the basal ganglia, and also in different
compartments within the cell (pre and post synaptic), we need to investigate if these effects are
caused by direct changes in medium spiny neurons, or by changes in the circuit, for example by
modulation of fast-spiking striatal interneurons or large aspiny cholinergic interneurons.
Disclosures: J.M. Burkhardt, None; R.M. Costa, None.