[Abstract Title]. - Society for Neuroscience

292. Acetylcholine, Neurotrophins, and Cognition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 292.7/SS20
Topic: F.02.d. Cognitive learning and memory systems
Support: Wellcome Trust
MRC UK
Title: Cholinergic depletion of the inferior temporal cortex interferes with recovery from
episodic memory deficits
Authors: *P. L. CROXSON, P. G. F. BROWNING, D. GAFFAN, M. G. BAXTER;
Dept Exptl. Psychol, Univ. of Oxford, Oxford, United Kingdom
Abstract: 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