Symposium
Session Room 213
Session Room 213
Monday, June 16, 02:40 PM – 03:55 PM
Symposium 5: New roles for neuromodulation in cognitive function and related disorders
Integrating cognitive and emotional processes is necessary for our behavior to remain adaptive. Dysfunction of this integrative capacity may contribute to major psychiatric and neurological conditions, such as schizophrenia, post-traumatic disorder (PTSD), addiction, and Alzheimer’s disease (AD). This symposium describes recent research using a variety of rodent model systems that reveal (i) roles of endocannabinoid system in modulating cognition and emotional responses associated with fear, (ii) a feedback inhibitory circuit in the brain that modulates cognitive control of goal-directed action, and (iii) roles of dopamine-cAMP signals in modulating memory retrieval and updating. In doing so, we will reveal new and exciting insights that help elucidate the processes in the brain that modulate cognitive and emotional integration.
Bernard Balleine will describe a modulatory circuit that mediates the cognitive control of choice and decision-making. Predictive learning can engage a form of cognitive control that biases choice between actions based on the information about future outcomes that learning provides. This influence has been hypothesized to depend on a feedback circuit in the brain through which the basal ganglia modulate activity in the prefrontal cortex. He will describe research revealing that the influence of predictive learning on decision-making is mediated by an inhibitory feedback circuit linking the medial ventral pallidum and mediodorsal thalamus. Activity of this circuit causes disinhibition of the orbitofrontal cortex via the inhibition of inhibitory parvalbumin interneurons during choice. This research suggests, therefore, that the mediodorsal thalamus serves as a pallidal-cortical relay through which predictive learning controls action selection, with important implications for understanding cognitive control and its vicissitudes in various psychiatric disorders and addiction.
Andrew Holmes will describe work employing in vivo optogenetics, eCB biosensor imaging, ex vivo electrophysiology, and CRISPR-Cas9 gene editing in mice examining whether basolateral amygdala (BLA)-projecting medial prefrontal cortex (mPFC) neurons represent a neural substrate for the effects of eCBs on extinction. He will show that photoexcitation of mPFC axons in BLA during extinction mobilizes BLA eCBs, that eCBs exhibit a dynamic stimulus-specific pattern of activity at mPFC→BLA neurons that tracks extinction, and that extinction memory formation involves eCB activity at cannabinoid CB1 receptors expressed at vmPFC→BLA synapses. His findings reveal the temporal characteristics and a neural circuit basis of eCBs' effects on fear extinction and inform efforts to target the eCB system as a therapeutic approach in extinction-deficient neuropsychiatric disorders.
Finally, Satoshi Kida, a chair of this symposium, will describe the roles of dopamine-cAMP signals in the modulation of retrieval and retrieved memory in mice. He found that dopamine-cAMP signal transduction is downregulated in the mouse model, showing retrieval deficits that exhibit impaired forebrain circadian clocks. This mouse model shows reductions of expression of adenylate cyclase 1 and dopamine 1 and 5 receptors and cAMP contents in the hippocampus, suggesting dysfunction of dopamine-cAMP signals. Furthermore, he showed that this signal transduction positively regulates retrieval and reconsolidation using optogenetics and pharmacology. His findings suggest that the upregulation of cAMP signals is potentially involved in PTSD, addiction, and chronic pain, whereas this downregulation may contribute to AD.
Bernard Balleine will describe a modulatory circuit that mediates the cognitive control of choice and decision-making. Predictive learning can engage a form of cognitive control that biases choice between actions based on the information about future outcomes that learning provides. This influence has been hypothesized to depend on a feedback circuit in the brain through which the basal ganglia modulate activity in the prefrontal cortex. He will describe research revealing that the influence of predictive learning on decision-making is mediated by an inhibitory feedback circuit linking the medial ventral pallidum and mediodorsal thalamus. Activity of this circuit causes disinhibition of the orbitofrontal cortex via the inhibition of inhibitory parvalbumin interneurons during choice. This research suggests, therefore, that the mediodorsal thalamus serves as a pallidal-cortical relay through which predictive learning controls action selection, with important implications for understanding cognitive control and its vicissitudes in various psychiatric disorders and addiction.
Andrew Holmes will describe work employing in vivo optogenetics, eCB biosensor imaging, ex vivo electrophysiology, and CRISPR-Cas9 gene editing in mice examining whether basolateral amygdala (BLA)-projecting medial prefrontal cortex (mPFC) neurons represent a neural substrate for the effects of eCBs on extinction. He will show that photoexcitation of mPFC axons in BLA during extinction mobilizes BLA eCBs, that eCBs exhibit a dynamic stimulus-specific pattern of activity at mPFC→BLA neurons that tracks extinction, and that extinction memory formation involves eCB activity at cannabinoid CB1 receptors expressed at vmPFC→BLA synapses. His findings reveal the temporal characteristics and a neural circuit basis of eCBs' effects on fear extinction and inform efforts to target the eCB system as a therapeutic approach in extinction-deficient neuropsychiatric disorders.
Finally, Satoshi Kida, a chair of this symposium, will describe the roles of dopamine-cAMP signals in the modulation of retrieval and retrieved memory in mice. He found that dopamine-cAMP signal transduction is downregulated in the mouse model, showing retrieval deficits that exhibit impaired forebrain circadian clocks. This mouse model shows reductions of expression of adenylate cyclase 1 and dopamine 1 and 5 receptors and cAMP contents in the hippocampus, suggesting dysfunction of dopamine-cAMP signals. Furthermore, he showed that this signal transduction positively regulates retrieval and reconsolidation using optogenetics and pharmacology. His findings suggest that the upregulation of cAMP signals is potentially involved in PTSD, addiction, and chronic pain, whereas this downregulation may contribute to AD.
02:40 PM – 03:05 PM
25 min
25 min