Cholinergic modulation of midbrain dopaminergic systems.

Mena-Segovia J
Winn P
Bolam JP
Scientific Abstract

Dopamine neurons in the midbrain respond to behavioral events and environmental stimuli. Their different patterns of activation in turn modulate the activity of forebrain regions and modulate the expression of selective behavioral responses. However, their activity is closely dependent on the cholinergic systems in the brainstem. Ascending cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei target dopaminergic neurons in the substantia nigra compacta and ventral tegmental area following a topographical gradient. These projections, by means of the activation of acetylcholine receptors, influence the firing of dopamine neurons and therefore their responsiveness, ultimately affecting the release of dopamine in their forebrain targets. Brainstem cholinergic neurons are thus in a position to critically influence the activity of dopaminergic neurons in the midbrain, and thereby have a critical role in the expression of behavior.


2008.Brain Res Rev, 58(2):265-71.

Duszkiewicz AJ, McNamara CG, Takeuchi T, Genzel L
2019. Trends Neurosci., 42(2):102-114.
Fischer P, Chen CC, Chang YJ, Yeh CH, Pogosyan A, Herz DM, Cheeran B, Green AL, Aziz TZ, Hyam J, Little S, Foltynie T, Limousin P, Zrinzo L, Hasegawa H, Samuel M, Ashkan K, Brown P, Tan H
2018. J. Neurosci., 38(22):5111-5121.
Perera T, Tan JL, Cole MH, Yohanandan SAC, Silberstein P, Cook R, Peppard R, Aziz TZ, Coyne TJ, Brown P, Silburn PA, Thevathasan W
2018. Brain, 141(10):3009-3022.
Torrecillos F, Tinkhauser G, Fischer P, Green AL, Aziz TZ, Foltynie T, Limousin P, Zrinzo L, Ashkan K, Brown P, Tan H
2018. J. Neurosci., 38(41):8905-8917.
Weinrich CA, Brittain JS, Nowak M, Salimi-Khorshidi R, Brown P, Stagg CJ
2017. Curr. Biol., 27:3061-3068.