Biology subjects

Nolen, H. G.

Publications and source records attributed to Nolen, H. G..

3 recordsLinked to original sources

bioRxiv2023

Locus Coeruleus Norepinephrine Neurons Facilitate Orbitofrontal Cortex Remapping and Behavioral Flexibility

To guide behavior, brain regions such as the orbitofrontal cortex (OFC) retain complex information about current tasks and expected outcomes in cellular representations referred to as cognitive maps. When actions produce undesirable results, OFC cognitive maps must update to promote behavioral change. Here, we show that this remapping is driven by the locus coeruleus (LC), a small brainstem nucleus that contains most of the brains norepinephrine (NE)-releasing neurons. In a task that tests behavioral flexibility in rodents, LC-NE activity correlated with task acuity and altered depending on trial outcome. Silencing LC neurons caused perseverative behavior and impeded cognitive remapping in OFC, while enhancing LC activity disrupted the ability of new maps to stabilize. These findings reveal a novel role for bidirectional LC-NE signaling in regulation of OFC cognitive map stability and promotion of flexible behavior that differs from the traditional function of this circuit as a global arousal signal.

neuroscience↗

bioRxiv2020

Chronic Effects of Indirect and Direct Cannabinoid Receptor Agonists on Addiction-Related Behaviors and Dopamine Release

The cannabinoid system is being researched as a potential pharmaceutical target for a multitude of disorders. The present study examined the effect of indirect and direct cannabinoid agonists on mesolimbic dopamine release and related behaviors in C57BL/6J (B6) mice. The indirect cannabinoid agonist N-arachidonoyl serotonin (AA-5-HT) indirectly agonizes the cannabinoid system by preventing the metabolism of endocannabinoids through fatty acid amide hydrolase (FAAH) inhibition while also inhibiting transient receptor potential vanilloid type 1 (TRPV1) channels. Effects of AA-5-HT were compared with the direct cannabinoid receptor type 1 (CB1R) agonist arachidonoyl-2-chloroethylamide (ACEA). In Experiment 1, mice were pretreated with 7 daily injections of AA-5-HT, ACEA, or vehicle prior to assessments of locomotor activity using open field (OF) testing and phasic dopamine release using in vivo fixed potential amperometry. Chronic exposure to AA-5-HT did not alter locomotor activity or mesolimbic dopamine functioning. Chronic exposure to ACEA did not alter locomotor activity but did decrease phasic dopamine release while increasing the dopaminergic response to cocaine. In Experiment 2, mice underwent AA-5-HT, ACEA, or vehicle conditioned place preference (CPP) then saccharin preference testing, a measure commonly associated with anhedonia. Mice did not develop a CPP or aversion for AA-5-HT or ACEA, and repeated exposure to AA-5-HT or ACEA did not alter saccharin preference. Altogether, the findings suggest that neither of these drugs induce behaviors that are classically associated with abuse liability in mice; however, direct CB1R agonism may play more of a role in mediating mesolimbic dopamine functioning than indirect cannabinoid agonism.

neuroscience↗

bioRxiv2019

Cerebellar Modulation of Mesolimbic Dopamine Transmission is Functionally Asymmetrical

Cerebral and cerebellar hemispheres are known to be asymmetrical in structure and function, and previous literature supports that asymmetry extends to the neural dopamine systems. Using in vivo fixed-potential amperometry with carbon-fiber microelectrodes in anesthetized mice, the current study assessed hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this reward-associated pathway. Our results suggest that cerebellar output can modulate mesolimbic dopamine transmission, and this modulation contributes to asymmetrically lateralized dopamine release. Dopamine release did not differ between hemispheres when evoked by medial forebrain bundle (MFB) stimulation; however, dopamine release was significantly greater in the right NAc relative to the left when evoked by electrical stimulation of the cerebellar dentate nucleus (DN). Furthermore, cross-hemispheric talk between the left and right cerebellar DN does not seem to influence mesolimbic release given that lidocaine infused into the DN opposite to the stimulated DN did not alter release. These studies may provide a neurochemical mechanism for studies identifying the cerebellum as a relevant node for reward, motivational behavior, saliency, and inhibitory control. An increased understanding of the lateralization of dopaminergic systems may reveal novel targets for pharmacological interventions in neuropathology of the cerebellum and extending projections.

neuroscience↗