Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity

Abstract

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.

A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease

“…The dopaminergic system plays a core role in the regulation of goal-directed and motivating effortful behavior for reward, and its dysfunction has been proposed to play a crucial role in the etiology of apathy in PD ( 31 ). In this line, there is remarkable evidence regarding the involvement of the mesolimbic system and structures such as the nucleus accumbens—which play a central role in motivation—in the etiology of apathy in PD ( 1 , 32 , 33 ).…”

Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing

“…Furthermore, we can also use sensory cues as conditioned stimuli to induce conditioning via reinforcement or punishment ( Figure 2 (Cc)). Thus, brain-wide fMRI can identify the neural networks involved in emotion, motivation, prediction, and learning [ 32 , 33 , 34 ].…”

“…In addition, the mPFC has a bidirectional effect on the dopamine-related motivation levels depending on the frequency of stimulation [ 34 , 54 , 55 ]. Optogenetic self-stimulation of mPFC (AAV-hSyn-ChR2 into IL; 25 Hz) serves as a reward in rodents and induces positively reinforced behaviors for receiving optogenetic stimulation [ 34 , 54 ].…”

“…In addition, the mPFC has a bidirectional effect on the dopamine-related motivation levels depending on the frequency of stimulation [ 34 , 54 , 55 ]. Optogenetic self-stimulation of mPFC (AAV-hSyn-ChR2 into IL; 25 Hz) serves as a reward in rodents and induces positively reinforced behaviors for receiving optogenetic stimulation [ 34 , 54 ]. Activation of the IL (25Hz) increased fMRI responses in multiple motivation-related regions, including the anterior insular area, anterior thalamus, ventral striatum, and hypothalamus, which were positively correlated with the level of reinforced behaviors [ 34 , 54 ].…”

“…Optogenetic self-stimulation of mPFC (AAV-hSyn-ChR2 into IL; 25 Hz) serves as a reward in rodents and induces positively reinforced behaviors for receiving optogenetic stimulation [ 34 , 54 ]. Activation of the IL (25Hz) increased fMRI responses in multiple motivation-related regions, including the anterior insular area, anterior thalamus, ventral striatum, and hypothalamus, which were positively correlated with the level of reinforced behaviors [ 34 , 54 ]. On the other hand, continuous activation of the IL with step-function opsin suppressed both reward-related behavior and the striatal fMRI response to stimulation of midbrain dopaminergic neuron [ 55 ].…”