Basal Forebrain Cholinergic System And Gamma-Aminobutyric Acid System: Implication In Cognitive Decline And Neuropsychological Impairment

The Basal Forebrain Cholinergic System and Its Role in Cognitive Function

The basal forebrain cholinergic system is primarily involved in the onset of different signs and symptoms in the patient Pat. Some of the signs and symptoms indicated by Pat comprise of an interruption in thoughts and reasoning, gradual loss of memory, addiction to cigarettes, difficulty in comprehending the information conveyed, depression, agitation and mobility impairment.

The structure of basal forebrain is located in front of the striatum and comprises of the nucleus accumbens, substantia innominate, diagonal band of Broca, nucleus basalis, and medial septal nucleus (Paul et al., 2015). According to Ballinger et al. (2016) the basal forebrain cholinergic system has been found imperative in the development of the system owing to the fact that they play a vital role in the synthesis of acetylcholine, a neurotransmitter that is widely distributed in the brain. The two main regions are cited below:

• When working together with the medial septum nucleus and the septum pellucidum, the diagonal band of Broca takes part in theta wave generation, thus governing the functions of the Hippocampus, most of which are related to emotion regulation, spatial navigation and memory(Catani, Dell’Acqua& De Schotten, 2013).
• Another cholinergic system, the nucleus basalis is responsible for the loss of attention in the patient since it promotes sustained attention (Gratwicke et al., 2013). Cholinergic neurons of this structure moderate the relation of different components of visual perception.

The main types of cholinergic receptors are:

• Nicotinic acetylcholine receptors- They are also referred to as nAChRand ionotropic acetylcholine receptors, these are chiefly responsive to acetylcholine and nicotine (Wonnacott et al., 2018).
• Muscarinic acetylcholine receptors- They are also referred to as mAChRor metabotropic acetylcholine receptors and are responsive to muscarin, the natural product found in mushrooms, apart from acetylcholine (Kruse et al., 2014).

nAChR modulates the neurobiological processes that control the hippocampal function of memory and learning. Nicotine has the ability to deaden (here deaden used to denote inactivity of the receptors) and upregulate definite nAChRs, thus altering the hippocampus reliant memory processes. On the other hand, the mAChR controls the formation of episodic memories.

Some of the drugs that can be administered to Pat are:

• Central depressants such as, barbiturates and benzodiapines will inhibit monoaminergic activity or facilitate GABA, thus modifying the electrical signalling and reducing the signs of depression in the patient (Jeffery et al., 2014).
• Psychotherapeutic drugs will also prove beneficial in treating the mood and behaviour of Pat and will produce their impact by blocking the receptors or inhibiting the transporters. Two common psychotherapeutic drugs are Prozac and Thorazine (Chlorpromazine).

Another potential neurotransmitter system that is relevant in Pat’s case is the Gamma-aminobutyric acid (GABA) system. Most of the GABA is synthesised for glutamate decarboxylation that is catalysed by glutamate decarboxylase. Upon release into the synaptic cleft, the GABA is taken by and converted to glutamine by the astrocyte cells. GABA transaminase catalyses the reaction. This neurotransmitter system comprises of three kinds of GABAergic receptors namely, 1) GABA_A, 2) GABA_B, 3)GABA_C.

Owing to the fact that the GABA neurotransmitter functions regulate significant cognitive functions, such as, attention and memory, it is imperative in the onset of the signs and symptoms that are reported by Pat. Furthermore, there exists a clear association between the GABA-ergic system and major depression. Research evidences have also correlated dysfunction in GABA to the onset of other psychiatric disorders such as, anxiety (Schüle, Nothdurfter&Rupprecht, 2014). Hence, owing to the fact that GABA plays a protuberant role in the control of strain, the most significantsusceptibility factor in attitude disorders, and deficits of the neurotransmitter are more pronounced in depression, the signs and symptoms reported by Pat can be correlated with the system (Fatemi et al., 2013).

My role as a healthcare worker would require me to involve Pat’s family members in the car process. I would try to explain to them that with an increase in age, the functions of the neurons that are the primary units of our brain start deteriorating and often get disrupted due to the action of different chemical pathways that occur in our brain.

I would create a pamphlet or leaflet that would contain the names of the all the neurotransmitter system that are governing the cognitive functions (memory, reasoning, attention) and would also help them understand about the potential benefits of the drugs that are intended to be administered. I would also take their consent regarding their values and preferences, in relation to the kind of treatment that I intend to deliver.

References

Ballinger, E. C., Ananth, M., Talmage, D. A., & Role, L. W. (2016). Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron, 91(6), 1199-1218.

Catani, M., Dell’Acqua, F., & De Schotten, M. T. (2013). A revised limbic system model for memory, emotion and behaviour. Neuroscience &Biobehavioral Reviews, 37(8), 1724-1737.

Fatemi, S. H., Folsom, T. D., Rooney, R. J., &Thuras, P. D. (2013). Expression of GABA A α2-, β1-and ?-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Translational psychiatry, 3(9), e303.

Gratwicke, J., Kahan, J., Zrinzo, L., Hariz, M., Limousin, P., Foltynie, T., &Jahanshahi, M. (2013). The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia?. Neuroscience &Biobehavioral Reviews, 37(10), 2676-2688.

Jeffery, D. D., May, L., Luckey, B., Balison, B. M., &Klette, K. L. (2014). Use and abuse of prescribed opioids, central nervous system depressants, and stimulants among US active duty military personnel in FY 2010. Military medicine, 179(10), 1141-1148.

Kruse, A. C., Kobilka, B. K., Gautam, D., Sexton, P. M., Christopoulos, A., &Wess, J. (2014). Muscarinic acetylcholine receptors: novel opportunities for drug development. Nature reviews Drug discovery, 13(7), 549.

Paul, S., Jeon, W. K., Bizon, J. L., & Han, J. S. (2015). Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Frontiers in aging neuroscience, 7, 43.

Schüle, C., Nothdurfter, C., &Rupprecht, R. (2014). The role of allopregnanolone in depression and anxiety. Progress in neurobiology, 113, 79-87.

Wonnacott, S., Bermudez, I., Millar, N. S., &Tzartos, S. J. (2018). Nicotinic acetylcholine receptors. British journal of pharmacology, 175(11), 1785-1788.