Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jan;91(1):13-22.
doi: 10.1016/j.nlm.2008.09.008. Epub 2008 Oct 26.

Acetylcholine activity in selective striatal regions supports behavioral flexibility

Michael E Ragozzino  1 , Eric G Mohler, Margaret Prior, Carlos A Palencia, Suzanne Rozman
Affiliations

Acetylcholine activity in selective striatal regions supports behavioral flexibility

Michael E Ragozzino et al. Neurobiol Learn Mem. 2009 Jan.

Abstract

Daily living often requires individuals to flexibly respond to new circumstances. There is considerable evidence that the striatum is part of a larger neural network that supports flexible adaptations. Cholinergic interneurons are situated to strongly influence striatal output patterns which may enable flexible adaptations. The present experiments investigated whether acetylcholine actions in different striatal regions support behavioral flexibility by measuring acetylcholine efflux during place reversal learning. Acetylcholine efflux selectively increased in the dorsomedial striatum, but not dorsolateral or ventromedial striatum during place reversal learning. In order to modulate the M2-class of autoreceptors, administration of oxotremorine sesquifumurate (100 nM) into the dorsomedial striatum, concomitantly impaired reversal learning and an increase in acetylcholine output. These effects were reversed by the m(2) muscarinic receptor antagonist, AF-DX-116 (20 nM). The effects of oxotremorine sesquifumurate and AF-DX-116 on acetylcholine efflux were selective to behaviorally-induced changes as neither treatment affected acetylcholine output in a resting condition. In contrast to reversal learning, acetylcholine efflux in the dorsomedial striatum did not change during place acquisition. The results reveal an essential role for cholinergic activity and define its locus of control to the dorsomedial striatum in cognitive flexibility.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Location of microdialysis probes in the dorsomedial, dorsolateral and ventromedial striatum of rats included in the analyses for Experiments 1-4. The length of the microdialysis probe was 2 mm. The number of probes does not match the total number of probe placements for rats included in the analyses because some probe placements overlapped to such a large extent that a single line represents more than one probe placement. The sections range from 0.3-to 1.7 mm in the anterior-posterior plane relative to bregma. The rat brain sections were modified from the atlas of Paxinos and Watson (1996).
Figure 2
Figure 2
Dorsomedial striatal ACh output and behavioral performance during place reversal learning. Each rat was tested for 30 minutes across five 6-min test blocks (T1-T5). (a) ACh output from the dorsomedial striatum during place reversal learning. Controls (aCSF) displayed an increase in ACh efflux of ∼ 50%. Oxotremorine sesquifumurate 100 nM infused into the dorsomedial striatum significantly reduced ACh compared to that of controls output throughout the reversal learning period. AF-DX-116 20 nM infused into the dorsomedial striatum led to a change in ACh output comparable to that of aCSF controls. AF-DX-116 20 nM infused in combination with oxotremorine sesquifumurate 100 nM elevated ACh efflux to level of aCSF controls. (b) Mean percent correct during place reversal learning. All groups performed at ∼ 85-90% correct on the final block of place acquisition (ACQ). Subsequently, all groups dropped to 40-50% on the first reversal learning block (T1). Oxotremorine sesquifumurate significantly reduced performance on blocks T2-T5 compared to that of all other groups. AF-DX-116 combined with oxotremorine sesquifumurate led to reversal learning performance that was not significantly different from that of controls.
Figure 3
Figure 3
Number of trials completed per block during reversal learning. Controls, oxotremorine sesquifumurate 100 nM, AF-DX-116 20 nM and the combination of oxotremorine sesquifumurate and AF-DX-116 infused into the dorsomedial striatum led to a comparable number of trials completed across all five blocks of reversal learning.
Figure 4
Figure 4
Effect of oxotremorine sesquifumurate 100 nM and AF-DX-116 20 nM infused into the dorsomedial striatum on ACh efflux in a resting condition. Samples were collected at 6-min intervals. Infusion of either drug did not affect basal ACh output.
Figure 5
Figure 5
Effect of place acquisition testing on dorsomedial striatal ACh output. Each rat was tested for four 6-min blocks (a) ACh output did not change compared to baseline levels during behavioral testing. (b) Mean percent correct during place acquisition testing. Rats performed slightly above chance levels (chance = 50%) at the first test block and improved to ∼ 85% by the last test block.
Figure 6
Figure 6
Effect of place reversal learning on dorsolateral and ventromedial striatal ACh output. Each rat was tested for five 6-min blocks during reversal learning. (a) ACh output did not change compared to baseline levels in the dorsolateral or ventromedial striatum during place reversal learning. (b) Mean percent correct during place reversal learning. Both groups had ∼ 90% accuracy on the last block of place acquisition and subsequently dropped to chance levels during the first block of reversal learning and achieved ∼ 90% accuracy by the last test block of reversal learning.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alcantara AA, Mrzljak L, Jakab RL, Levey AI, Hersch SM, Goldman-Rakic PS. Muscarinic m1 and m2 receptor proteins in local circuit and projection neurons of the primate striatum: anatomical evidence for cholinergic modulation of glutamatergic prefronto-striatal pathways. J Comp Neurol. 2001;434:445–460. - PubMed
    1. Aosaki T, Tsubokawa H, Ishida A, Watanabe K, Graybiel AM, Kimura M. Responses of tonically active neurons in the primate's striatum undergo systematic changes during behavioral sensorimotor conditioning. J Neurosci. 1994;6:3969–3984. - PMC - PubMed
    1. Apicella P. Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events. Euro J Neurosci. 2002;16:2017–2026. - PubMed
    1. Bertorelli R, Forloni G, Consolo S. Modulation of cortical in vivo acetylcholine release by the basal nuclear complex: role of the pontomesencephalic tegmental area. Brain Res. 1991;563:353–356. - PubMed
    1. Birrell JM, Brown VJ. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci. 2000;20:4320–4324. - PMC - PubMed

Publication types

MeSH terms

  NODES
admin 1
INTERN 2
Project 1
twitter 2