Differential Modulation of Nucleus Accumbens Synapses
by
James M. Brundege and John T. Williams
The Vollum Institute,
Oregon Health and Science University,
Portland, Oregon 97201
The Journal of Neurophysiology Vol. 88 No. 1 July 2002

ABSTRACT

The nucleus accumbens (NAcc) is a brain region involved in functions ranging from motivation and reward to feeding and drug addiction. The NAcc is typically divided into two major subdivisions, the shell and the core. The primary output neurons of both of these areas are medium spiny neurons (MSNs), which are quiescent at rest and depend on the relative input of excitatory and inhibitory synapses to determine when they fire action potentials. These synaptic inputs are, in turn, regulated by a number of neurochemical signaling agents that can ultimately influence information processing in the NAcc. The present study characterized the ability of three major signaling pathways to modulate synaptic transmission in NAcc MSNs and compared this modulation across different synapses within the NAcc. The opioid [Met]5enkephalin (ME) inhibited excitatory postsynaptic currents (EPSCs) in shell MSNs, an effect mediated primarily by µ-opioid receptors. Forskolin, an activator of adenylyl cyclase, potentiated shell EPSCs. An analysis of miniature EPSCs indicated a primarily presynaptic site of action, although a smaller postsynaptic effect may have also contributed to the potentiation. Adenosine and an adenosine A1-receptor agonist inhibited shell EPSCs, although no significant tonic inhibition by endogenous adenosine was detected. The effects of these signaling agents were then compared across four different synapses in the NAcc: glutamatergic EPSCs and GABAergic inhibitory postsynaptic currents (IPSCs) in both the core and shell subregions. ME inhibited all four of these synapses but produced a significantly greater inhibition of shell IPSCs than the other synapses. Forskolin produced an increase in transmission at each of the synapses tested. However, analysis of miniature IPSCs in the shell showed no sign of a postsynaptic contribution to this potentiation, in contrast to the shell miniature EPSCs. Tonic inhibition of synaptic currents by endogenous adenosine, which was not observed in shell EPSCs, was clearly present at the other three synapses tested. These results indicate that neuromodulation can vary between the different subregions of the NAcc and between the different synapses within each subregion. This may reflect differences in neuronal interconnections and functional roles between subregions and may contribute to the effects of drugs acting on these systems.

D1
MDMA
Selegiline
Dopamine
Amineptine
Tranylcypromine
Dopamine and sex
Why is cannabis fun?
The hedonic treadmill
The taste of happiness
Adenosine and the nucleus accumbens
Dopamine and dopaminergic antidepressants
Pain, motivation, pleasure and the rostral shell
Depression, dopamine and dextroamphetamine
Mesolimbic medium spiny neurons and pleasure
The nucleus accumbens: opioids versus cannabinoids
GABA, opiates, happiness and the nucleus accumbens
Hedonic zonal shifts in the medial shell of the nucleus accumbens

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