Acetylcholine is a neuromodulator that plays a variety of roles in the central nervous system and is highly implicated in visual perception and visual cortical plasticity. Visual sequence learning, defined here as the ability to encode and predict the spatiotemporal content of visual information, has been shown to depend on muscarinic signaling in the mouse primary visual cortex (V1). Muscarinic signaling is a complex process involving the combined activities of five different G-protein coupled receptors, M1-M5, all of which are expressed in the murine brain but differ from each other functionally and in anatomical localization. While previous work has isolated the required signaling to V1, it is unknown which muscarinic receptors are required for spatiotemporal sequence learning.
We hypothesized that M1 or M2 receptors are required for sequence learning since they are known to be abundantly expressed in rodent V1.
Our aim was to identify the muscarinic receptor required for sequence learning using electrophysiology, followed by immunofluorescence to determine the anatomical distribution of the identified receptor in V1 in a layer-wise and cell-type fashion. Another aim was to better tease out the timing of muscarinic activity required for encoding the visual sequence.
Here we present electrophysiological evidence that M2, but not M1, receptors are required for spatiotemporal sequence learning in mouse V1. We show that M2 is highly expressed in the neuropil in V1, especially in thalamorecipient layer 4, and co-localizes to the soma of a subset of somatostatin expressing neurons in deep layers. We also show that expression of M2 receptors is higher in the monocular region of V1 than it is in the binocular region, but that the amount of experience-dependent sequence potentiation is similar in both regions. Finally, we show that interrupting mAChR activity after visual stimulation does not prevent sequence potentiation. This work establishes a new functional role for M2-type receptors in processing temporal information and demonstrates that monocular circuits are modified by experience in a manner like binocular circuits.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47012 |
| Date | 22 September 2023 |
| Creators | Sarkar, Susrita |
| Contributors | Gavornik, Jeffrey |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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