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GABAergic control of dopaminergic ne...

Paladini, Carlos Antonio.

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GABAergic control of dopaminergic neuron activity.

Record Type:	Electronic resources : Monograph/item
Title/Author:	GABAergic control of dopaminergic neuron activity./
Author:	Paladini, Carlos Antonio.
Description:	205 p.
Notes:	Source: Dissertation Abstracts International, Volume: 60-05, Section: B, page: 2015.
Contained By:	Dissertation Abstracts International60-05B.
Subject:	Biology, Neuroscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9929703
ISBN:	0599298383

GABAergic control of dopaminergic neuron activity.
Paladini, Carlos Antonio.

GABAergic control of dopaminergic neuron activity. - 205 p.

Source: Dissertation Abstracts International, Volume: 60-05, Section: B, page: 2015.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - Newark, 1999.

Pathophysiology of the dopaminergic neurons of the substantia nigra pars compacta (SNC) underlies many of the symptoms of neurological disorders such as Parkinson's disease. These neurons and their synaptic targets also serve as the sites of action of stimulant drugs of abuse such as cocaine. Dopamine neurons fire in three patterns, namely random, pacemaker, and bursty firing pattern. The different firing patterns, especially the bursty pattern, of the nigrostriatal neurons of the SNC have been correlated with environmental stimuli relevant to reward contingencies. Also spikes of dopaminergic neurons of the SNC clustered in bursts may result in more dopamine at synaptic targets than single spikes. The fact that these cells fire differently in vitro than in vivo suggests that the afferent control of these neurons is critically involved in the regulation of their firing pattern. NMDA receptor activation has been implicated in the control of the bursty firing pattern of dopaminergic neurons. However up to 90% of all inputs to SNC are GABAergic and modulation of dopaminergic neurons may be controlled through disinhibition. The receptors mediating the inhibitory effects resulting from stimulation of the striatum (Str), globus pallidus (GP), and substantia nigra pars reticulata (SNR) projection neurons have been determined to be due to GABAA receptor activation. The effects of GABAA and GABAB receptor blockade on the spontaneous activity of dopaminergic neurons were also determined. GABAA receptor blockade evoked a shift to a bursty pattern whereas GABAB receptor activation showed only a modest shift to a pacemaker pattern. This was demonstrated using extracellular recordings in combination with local application of selective antagonists for different receptors. Also pharmacological manipulation of GP has demonstrated that the SNR provides a significant influence on the firing pattern of dopaminergic neurons. The hypothesis that GABA suppresses bursting by decreasing the input resistance of the neuron thereby making the dendritic arbor electrotonically longer, rather than by hyperpolarization was tested. This was done using in vitro whole cell recordings and adjusting the chloride reversal potential so that GABA was either depolarizing or hyperpolarizing. Under these conditions GABA suppressed bursting even when it depolarized the neuron.

ISBN: 0599298383Subjects--Topical Terms:

1017680
Biology, Neuroscience.

GABAergic control of dopaminergic neuron activity.
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100 1 $a Paladini, Carlos Antonio. $3 1907175
245 1 0 $a GABAergic control of dopaminergic neuron activity.
300 $a 205 p.
500 $a Source: Dissertation Abstracts International, Volume: 60-05, Section: B, page: 2015.
500 $a Director: James M. Tepper.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - Newark, 1999.
520 $a Pathophysiology of the dopaminergic neurons of the substantia nigra pars compacta (SNC) underlies many of the symptoms of neurological disorders such as Parkinson's disease. These neurons and their synaptic targets also serve as the sites of action of stimulant drugs of abuse such as cocaine. Dopamine neurons fire in three patterns, namely random, pacemaker, and bursty firing pattern. The different firing patterns, especially the bursty pattern, of the nigrostriatal neurons of the SNC have been correlated with environmental stimuli relevant to reward contingencies. Also spikes of dopaminergic neurons of the SNC clustered in bursts may result in more dopamine at synaptic targets than single spikes. The fact that these cells fire differently in vitro than in vivo suggests that the afferent control of these neurons is critically involved in the regulation of their firing pattern. NMDA receptor activation has been implicated in the control of the bursty firing pattern of dopaminergic neurons. However up to 90% of all inputs to SNC are GABAergic and modulation of dopaminergic neurons may be controlled through disinhibition. The receptors mediating the inhibitory effects resulting from stimulation of the striatum (Str), globus pallidus (GP), and substantia nigra pars reticulata (SNR) projection neurons have been determined to be due to GABAA receptor activation. The effects of GABAA and GABAB receptor blockade on the spontaneous activity of dopaminergic neurons were also determined. GABAA receptor blockade evoked a shift to a bursty pattern whereas GABAB receptor activation showed only a modest shift to a pacemaker pattern. This was demonstrated using extracellular recordings in combination with local application of selective antagonists for different receptors. Also pharmacological manipulation of GP has demonstrated that the SNR provides a significant influence on the firing pattern of dopaminergic neurons. The hypothesis that GABA suppresses bursting by decreasing the input resistance of the neuron thereby making the dendritic arbor electrotonically longer, rather than by hyperpolarization was tested. This was done using in vitro whole cell recordings and adjusting the chloride reversal potential so that GABA was either depolarizing or hyperpolarizing. Under these conditions GABA suppressed bursting even when it depolarized the neuron.
590 $a School code: 0461.
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Biology, Animal Physiology. $3 1017835
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710 2 0 $a Rutgers The State University of New Jersey - Newark. $3 1017745
773 0 $t Dissertation Abstracts International $g 60-05B.
790 1 0 $a Tepper, James M., $e advisor
790 $a 0461
791 $a Ph.D.
792 $a 1999
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9929703