The Effects of Temporary Inactivation of the Core and the Shell Subregions of the Nucleus Accumbens on Prepulse Inhibition of the Acoustic Startle Reflex and Activity in Rats

Abstract

The nucleus accumbens can be dissociated into at least two subregions: a 'core' and a 'shell'. Using temporary chemical inactivation of these subregions, we investigated whether they are differentially involved in the regulation of prepulse inhibition (PPI) of the acoustic startle reflex and activity. For this purpose, rats were bilaterally implanted with guide cannulae aimed at either the core or the shell and infused with the GABA A receptor agonist muscimol (0.5 mg/0.2 ml per side). The control group consisted of vehicle infused and unoperated rats. To ascertain the region selectivity of the infusions, 0.2 ml of [ 3 H]muscimol was infused into either the core or the shell of an additional group of rats. The behavioral results demonstrated that in comparison to the control group, inactivation of the core led to a loss of the prepulse intensity dependency of PPI. Moreover, core inactivation resulted in akinesia directly after infusion, but in hyperactivity 24 and 72 h thereafter in contrast to the control group. In both experiments, inactivation of the shell was ineffective compared to controls. Analysis of the autoradiograms revealed that the spread of drug into the other subregion was minimal, supporting the region selectivity of the inactivation. These results lend further support to the existence of a functional dissociation between the core and the shell, with the former being preferentially involved in PPI and locomotion. The persistent hyperactivity after the muscimol infusion into the core could be explained by compensatory mechanisms taking place in the nucleus accumbens.

Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments

“…The present findings contribute to a larger body of work in which prolonged inactivation or lesions of the NAcc shell improve behavioral flexibility in various forms, including latent inhibition, Pavlovian-instrumental transfer, and attentional set-shifting (Weiner et al 1996;Corbit et al 2001;Pothuizen et al 2005a;Floresco et al 2006). For example, Floresco et al (2006) found that NAcc shell inhibition during the first day of discrimination learning led to improved performance (fewer trials to reach criterion) relative to controls receiving inhibition after a set switch.…”

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

“…Although GABAergic interneurons make up about 2% of all neurons in the NAc [41], GABA receptor agonists have been widely used to inactivate the NAc [42,43]. Infusion of one tenth of the regular doses of GABA receptor agonists into the NAcSh was effective in rescuing the novelty-seeking behavior of TLR4 -/-mice under motivational conflict.…”

Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders

“…The neuronal circuitry of PPI comprises limbic and cortico-pallido-striato-thalamic structures with the nucleus accumbens involved in a central mediatory influence (Kodsi and Swerdlow 1995;Fendt et al 2001;Pothuizen et al 2005) which, through the projection from the ventral pallidum to the pedunculopontine tegmental nucleus, modulates the primary startle circuitry in brainstem nuclei (Kretschmer and Koch 1998). The core of the nucleus accumbens projects to the entopeduncular nucleus which in turn projects to the pedunculopontine tegmental nucleus (Heimer et al 1991;Zahm and Heimer 1993).…”