Dopamine and Serotonin-Induced Modulation of GABAergic and Glutamatergic Transmission in the Striatum and Basal Forebrain

Abstract

Catecholamine receptor-mediated modulation of glutamatergic or GABAergic transmission in the striatum as well as basal forebrain (BF) has been intensively studied during these two decades. In the striatum, activation of dopamine (DA) D2 receptors in GABAergic terminals inhibits GABA release onto cholinergic interneurons by selective blockade of N-type calcium channels. In the BF, glutamatergic transmission onto cholinergic projection neurons is inhibited via DA D1-like receptors by selective blockade of P/Q-type calcium channels. On the other hand, presynaptic inhibition of the GABA release onto cholinergic neurons mediated by D1-like receptors or 5-HT1B receptors is independent of calcium influx. In addition, the DA receptor-mediated calcium influx dependent presynaptic inhibition mentioned above decreases with postnatal development, with selective coupling between DA receptors and each subtype of calcium channels being unchanged. Furthermore, the precise origin of these GABAergic or glutamatergic inputs to postsynaptic neurons can be identified by recent optogenetic approaches. Thus, modulatory mechanisms in specific synaptic connections between certain types of neurons in the striatum and BF are being identified.

A Cortical Pathogenic Theory of Parkinson’s Disease

“…Nigrostriatal input exerts not only the classic receptor-dependent post-synaptic neuromodulation of MSN excitability (Gerfen and Surmeier, 2011), but also pre-synaptic inhibition of glutamate striatal release via dopaminergic receptors on corticostriatal terminals in an activity-dependent fashion (Bamford et al, 2004). MSN excitability is also influenced and modulated by striatal cholinergic and GABAergic interneurons (Tepper et al, 2004;Faust et al, 2016), which control striatal output activity particularly in the sensorimotor striatum (Kulik et al, 2017) and are also modulated by dopaminergic input (Momiyama and Nishijo, 2017). Altogether, corticostriatal and nigrostriatal axons interact at the synaptic level forming a functional unit with MSNs and interneurons (Shipp, 2017).…”

Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

“…This recurrent lateral inhibition is well suited to synchronize ChINs to a degree necessary to elicit DA release. While the nature of the intermediate neuron is not yet known, it too appears to be modulated by DA, possibly through a D2 mediated inhibition of presynaptic terminals via N-type Calcium Channels, as demonstrated by Momiyama and Nishijo ( 2017 ). Taken together, these interactions point toward a spatio-temporal coordination of recurrent control between the cholinergic and dopaminergic systems.…”

Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain

“…The observed lower 5‐HIAA levels in the most rostral part of the PUT are contrasted by higher HVA in this part of the PUT and may indicate that the 5‐HT release is slowed down by higher dopaminergic activity. On the other hand, a positive correlation between molar 5‐HIAA/5‐HT ratios and GABA levels might be because of the inhibitory action of 5‐HT on GABA release via 5‐HT1B receptors increasing GABA tissue levels (Nishijo and Momiyama, ; Momiyama and Nishijo, ), which, based on our subregional analysis, seems to be only active in the ventral CN.…”