New study on nicotinic receptors and long-term memory could lead to more targeted and effective therapies for dementia

A new University of
Bristol study, which identifies how acetylcholine impacts learning and memory
by acting at different receptors, could prove significant in the drive to
develop more targeted and effective therapies for dementia.

Currently, the main
treatments for Alzheimer’s disease are drugs that increase levels of
acetylcholine in the brain. The University of Bristol paper, published today in
Cell Reports, describes the role two main types of nicotinic receptor (α7 and
α4β2 receptors) play in long-term memory retrieval and encoding – and the
impact of acetylcholine on these receptors.

Nicotinic
receptors, named after their sensitivity to nicotine, are expressed in the
human and rodent brain where they are naturally activated by the
neurotransmitter acetylcholine. Activation of nicotinic receptors by
acetylcholine in the frontal cortex of the brain has previously been shown to
be essential for functions such as attention and working memory.

Professor of
Cellular Neuroscience, Zafar
Bashir, and PHD student, Marie Sabec, in the School
of Physiology, Pharmacology and Neuroscience, have demonstrated for the
first time that both types of nicotinic receptor are essential for long-term
associative recognition in rats.

What’s more, the
study also found that each nicotinic receptor subtype was responsible for
distinct aspects of memory. The initial encoding of information (“learning”)
was dependent on the α7 nicotinic receptor, and subsequent memory retrieval
(“remembering”) relied on the α4β2 receptor.

Prof. Bashir
commented on the findings:

“Learning is
thought to rely on changes in the strength of communication between neurons. In
this study we have shown that the α7 nicotinic receptors enhance communication
between the hippocampus and frontal cortex but α4β2 nicotinic receptors
decrease communication between these regions. Therefore, acetylcholine
acting on different subtypes of nicotinic receptor in the frontal brain can
enhance or depress neural communication for the learning and remembering of
long-term memory, respectively.

“These findings
could have significant implications for the way stimulation of acetylcholine is
used to treat Alzheimer’s. If drugs can be developed to target the individual
nicotinic receptors, responsible for different aspects of long-term memory, we
could see much more targeted and effective therapies for dementia.”

Paper

The paper Nicotinic acetylcholine receptors
control encoding and retrieval of associative recognition memory through
plasticity in the medial prefrontal cortex by Sabec et al is published on 27 March 2018 in
Cell Reports.