Title:The Integration of Top-down and Bottom-up Inputs to the Striatal
Cholinergic Interneurons
Volume: 22
Issue: 9
Author(s): Yan-Feng Zhang*John N.J. Reynolds
Affiliation:
- Department of Anatomy, Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
- Department of Clinical and Biomedical Sciences, University of Exeter Medical School, Hatherly Laboratories, Exeter
EX4 4PS, United Kingdom
Keywords:
Cholinergic interneurons, firing pattern, pauses, top-down input, bottom-up input, integration.
Abstract:
Background: Cholinergic interneurons (ChIs) are important for learning and memory.
They exhibit a multiphasic excitation-pause-rebound response to reward or sensory cues indicating a
reward, believed to gate dopamine-dependent learning. Although ChIs receive extensive top-down inputs
from the cortex and bottom-up inputs from the thalamus and midbrain, it is unclear which inputs
are involved in the development of ChI multiphasic activity.
Methods: We used a single-unit recording of putative ChIs (pChIs) in response to cortical and visual
stimulation to investigate how top-down and bottom-up inputs regulate the firing pattern of ChIs.
Results: We demonstrated that cortical stimulation strongly regulates pChIs, with the maximum firing
rate occurring at the peak of the inverted local field potential (iLFP), reflecting maximum cortical
stimulation. Pauses in pChIs occurred during the descending phase of iLFP, indicating withdrawal of
excitatory cortical input. Visual stimulation induced long pauses in pChIs, but it is unlikely that bottom-
up inputs alone induce pauses in behaving animals. Also, the firing pattern of ChIs triggered by
visual stimulation did not correlate with the iLFP as it did after cortical stimulation. Top-down and
bottom-up inputs independently regulate the firing pattern of ChIs with similar efficacy but notably
produce a well-defined pause in ChI firing.
Conclusion: This study provides in vivo evidence that the multiphasic ChI response may require both
top-down and bottom-up inputs. The findings suggest that the firing pattern of ChIs correlated to the
iLFP might be a useful tool for estimating the degree of contribution of top-down and bottom-up inputs
in regulating the firing activity of ChIs.
