Dopamine and action potential generation in the axon initial segment

Dopamine is one of the principal neuromodulators in the brain acting on two large families of receptors, namely D1-like and D2-like. It is involved in several important cognitive and motor functions within different brain areas and it is strongly implicated in rewarding and addiction behaviours. In the medial entorhinal cortex (MEC), dopamine is believed to play a crucial role in the spatial cognition functions performed by this area of the brain (Hafting et al., 2005). In particular, type-2 dopamine receptors (D2Rs) appear to be involved in spatial cognition (Mehta et al., 2001) and stellate cells in the MEC contain high levels of D2Rs. Stellate cells in layer II of the MEC are classified as "grid cells" as they provide spatial information to the animal by spanning the environment. The axons of these neurons innervate the hippocampus forming excitatory synapses. Hence, the physiological pathway triggered by D2R activation in MEC stellate cells is likely fundamental for spatial cognition.