Biology subjects

Martyniuk, K. M.

Publications and source records attributed to Martyniuk, K. M..

3 recordsLinked to original sources

bioRxiv2021

Dopamine D2Rs Coordinate Cue-Evoked Changes in Striatal Acetylcholine Levels

In the striatum, acetylcholine (ACh) neuron activity is modulated co-incident with dopamine (DA) release in response to unpredicted rewards and reward predicting cues and both neuromodulators are thought to regulate each other. While this co-regulation has been studied using stimulation studies, the existence of this mutual regulation in vivo during natural behavior is still largely unexplored. One long-standing controversy has been whether striatal DA is responsible for the induction of the cholinergic pause or whether D2R modulate a pause that is induced by other mechanisms. Here, we used genetically encoded sensors in combination with pharmacological and genetic inactivation of D2Rs from cholinergic interneurons (CINs) to simultaneously measure ACh and DA levels after CIN D2R inactivation. We found that CIN D2Rs are not necessary for the induction of cue induced dips in ACh levels but regulate dip lengths and rebound ACh levels. Importantly, D2R inactivation strongly decreased the temporal correlation between DA and Ach signals not only at cue presentation but also during the intertrial interval. This points to a general mechanism by which D2Rs coordinate both signals. At the behavioral level D2R antagonism increased the latency to lever press, which was not observed in CIN-selective D2R knock out mice. This latency correlated with the cue evoked dip length supporting a role of the ACh dip and its regulation by D2Rs in motivated behavior. Overall, our data indicate that striatal DA coordinate phasic ACh and DA signals via CIN D2Rs which is important for the regulation of motivated behavior.

neuroscience↗

bioRxiv2020

Dopamine D2 receptors modulate the cholinergic pause and inhibitory learning

Cholinergic interneurons (CINs) in the striatum respond to salient stimuli with a multiphasic response, including a pause, in neuronal activity. Slice physiology experiments have shown the importance of dopamine D2 receptors (D2Rs) in regulating CIN pausing yet the behavioral significance of the CIN pause and its regulation by dopamine in vivo is still unclear. Here, we show that D2R upregulation in CINs of the nucleus accumbens (NAc) lengthens the pause in CIN activity ex vivo and enlarges a stimulus-evoked decrease in acetylcholine (ACh) levels during behavior. This enhanced dip in ACh levels is associated with a selective deficit in the learning to inhibit responding in a Go/No-Go task. Our data demonstrate, therefore, the importance of CIN D2Rs in modulating the CIN response induced by salient stimuli and points to a role of the pause in inhibitory learning. This work has important implications for brain disorders with altered striatal dopamine and ACh function, including schizophrenia and attention-deficit hyperactivity disorder (ADHD).

neuroscience↗

bioRxiv2020

Dopamine D2R upregulation in nucleus accumbens indirect pathway does not affect Pavlovian and Go/No-Go Learning

Ventral striatal dopamine is thought to be important for associative learning. Dopamine exerts its role via activation of dopamine D1 and D2 receptors in the ventral striatum. Upregulation of dopamine D2R in the indirect pathway of the nucleus accumbens (NAc) impairs incentive motivation via inhibiting synaptic transmission to the ventral pallidum. Here, we determined whether upregulation of D2Rs and the resulting impairment in indirect pathway function modulates associative learning in an auditory Pavlovian reward learning task as well as Go/No-Go learning in an operant based reward driven Go/No-Go task. We found that upregulation of D2Rs in indirect pathway neurons of the NAc did not affect Pavlovian learning or the extinction of Pavlovian responses, and neither did it alter No-Go learning. A delay in the Go component of the task however could indicate a deficit in learning though it may be attributed to locomotor hyperactivity of the mice. In combination with previously published findings our data suggest that D2Rs in the NAc core play a specific role in regulating motivation by balancing cost/benefit computations but do not necessarily affect associative learning.

animal behavior and cognition↗