Neuronal acetylcholine receptor subunit alpha-5

The α5 nAChR is located in various areas of the brain including the cortex, hippocampus, hypothalamus, inferior colliculus, medial habenula, olfactory bulb and striatum.

Cholinergic dysfunction during development causes attentional deficits observed in diseases such as schizophrenia, neurodevelopmental disorders, autism and epilepsy.

Through continuous exposure, dependence often occurs which is followed by withdrawal symptoms such as cravings, irritation, restlessness, sleep disturbances, weight gain, anxiety and difficulty concentrating.

[11] Other studies have shown that α5 nAChR null mice display fewer signs of dependency and reduced anxiety-like behaviors.

However, reintroduction of the alpha 5 subunit in the medial habenula in knockout mice restored normal levels of nicotine self-administration.

[14] Human studies have shown that people with a single nucleotide polymorphism (SNP) within the α5 nAChR encoding gene (CHRNA5, rs16969968) correlates with an increased risk of nicotine dependency and pleasure along with more heavy smoking.

[19] Attention is an important aspect of memory that allows for information to be held in the mind and maintain focus in the presence of distractions in order to achieve a goal directed behavior.

The structure most commonly associated with attention is the prefrontal cortex that mediates top down control of complex cognitive processes.

Researchers speculate that layer VI pyramidal neurons in the prefrontal cortex are important for holding attention in cognitively demanding tasks.

In vivo studies have shown that the presence of alpha5 subunits of nAChRs on layer VI pyramidal neurons in the PFC are important for visual attention.

[5] Interestingly, the deletion of alpha5 subunits in mice results in an upregulation of muscarinic acetylcholine receptors as an excitatory compensation response to circuitry dysfunction.

Studies have performed microdialysis in subjects as they formed attention tasks and found significantly increased acetylcholine efflux.

[24] Studies have shown that removing the alpha5 subunit in mice (α5 nAChR knockdown) increases nicotine intake which is rescued by reintroducing the gene.

[27] During high frequency vagal stimulation, α5 nAChR knockout mice experience impaired cardiac parasympathetic ganglionic transmission.