Figure 2.

Neuromodulation of MSNs. Schematic representing the convergence of dopamine (DA) and ACh modulation on excitatory inputs onto a dMSN in the dorsal striatum (DS). DA terminals modulate excitatory neurotransmission forming synapses onto the neck of MSN spines; through two molecular mechanisms involving DA and the co-released GABA. These DAergic input is modulated by presynaptic nAChRs and this cholinergic control can itself be fine-tuned via the presence of presynaptic D2Rs. Activation of D1Rs, that are coupled to the Gαs protein, leads to the production of cyclic adenosine monophosphate (cAMP) via the adenylate cyclase (AC). This promotes the protein kinase A (PKA) function, which phosphorylates DARPP32, indirectly driving an increase in neuronal excitability via the activation of Ca²⁺ channels and NMDA receptors as well as the inhibition of K⁺ channels.