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Cholinergic depletion of the inferior temporal cortex interferes with recovery from episodic memory deficits

Croxson PL, Browning PGF, Gaffan D, Baxter MG (2008) Cholinergic depletion of the inferior temporal cortex interferes with recovery from episodic memory deficits. Neuroscience 2008 Abstracts 292.7/SS20. Society for Neuroscience, Washington, DC.

Summary: Cholinergic innervation of the temporal lobe has been suggested to have a role in episodic memory, a function which is also disrupted by lesions or disconnections of the medial temporal lobe circuit. Acetylcholine may be necessary for the specific function of some brain regions. Alternatively, it may be necessary for cortical plasticity and remodeling in those conditions in which the animal has to adapt following new task demands or injury. To investigate the role of cholinergic projections to inferotemporal cortex in episodic memory, and how loss of these projections might interact with damage to other brain structures necessary for normal memory function, we trained monkeys preoperatively on object-in-place scene discrimination problems until they could rapidly learn many problems within a testing session. Because learning occurs rapidly, mostly in a single trial, and depends on the presentation of discrimination problems in unique background scenes, this task models key features of human episodic memory. For the first stage of the experiment, the monkeys then received either a fornix transection or mammillary body ablation, both of which are known to impair learning in this task. All of the monkeys were impaired at scene learning after fornix or mammillary body lesions compared to their preoperative performance, consistent with previous results. In the second stage of the experiment, the monkeys underwent a second surgery in which we used the immunotoxin ME20.4-saporin to selectively deplete cholinergic inputs to the inferotemporal cortex. We then re-tested the monkeys on scene learning, and they were no more impaired than they were after their first surgery. This result is in striking contrast to an earlier finding by our laboratory that the effect of fornix transection is greatly exacerbated by prior depletion of acetylcholine from inferotemporal cortex (Browning et al. 2008, in press). The key difference between these two experiments is the order in which the lesions were placed: cholinergic depletion of inferotemporal cortex before fornix transection results in severe amnesia, whereas severe amnesia does not occur if the lesions are sustained in the opposite order. This finding suggests that monkeys require acetylcholine in inferotemporal cortex in order to adjust to the effects of a fornix lesion on episodic memory. This is consistent with a role for cholinergic input to neocortex in cortical plasticity and remodelling, rather than a specific role in certain brain functions such as episodic memory.

Related Products: ME20.4-SAP (Cat. #IT-15)

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