Summary
Acetylcholine is an acetic acid and choline ester neurotransmitter, which plays a somatic nervous system. This chemical is released into the brain during learning and new memories acquisition, it facilitates NMDA receptors and protein activities involved in connecting brain nerve cells activities. The nicotinic and muscarinic acetylcholine receptors encode new memories and enhance the ability of the mind to remember and learn new information.
Synthesis of acetylcholine occurs in nerve cells located in the basal forebrain, which has a high concentration of neuron transmitters and cholinergic nerves to form a network. The acetylcholine pathway passing through the hippocampus and cortex transmits mediated signals involved in memory and learning (Leaderbrand et al., 2016). It also aids in sustaining attention by enhancing the perception of visual stimuli while the cholinergic pathway increases learning and memory.
Acetylcholine is generated from acetyl CoA and choline in a step catalyzed by choline acetyltransferase. Thereafter, the acetylcholinesterase enzyme found in between nerve cells synapsis digests the acetylcholine to form acetate and choline. The neurotransmitter’s activities facilitate learning and memory by increasing N-methyl-D-aspartate (NMDA) receptor’s actions in the brain. This is done through the blocking of the 4 SK channel known as the small conductance calcium-activated potassium channels, which regulates neurons’ hyperpolarization and influences synaptic plasticity.
The SK proteins act as barriers that inhibit the functioning of NMDA receptors. They also interfere with neuron ability to moderate signal transmission by limiting memory encoding in the brain. Acetylcholine facilitates receptor activity by removing the SK channel barrier and helping the brain to connect different parts of memories. It also enhances memory, mental alertness, good mood, focus, and concentration. These attributes are lost in people with cognitive impairments such as Alzheimer’s and dementia.
The memory functioning process has three main stages, which are encoding in the parietal lobes, consolidation, and retrieval. The acetylcholine separates these phases and hinders in between memories interference for easy retrieval. For instance, it suppresses synaptic transmission, which moderates the learning of new memories in the cortex and hippocampus. Consequently, hindering retrieval of old remembrances can interfere with new memories formation. Acetylcholine enables the storage of visual and verbal new information as memory, thus, it plays an important role in the learning process.
Involvement of Acetylcholine in Cognitive Decline in Alzheimer’s Disease
Alzheimer’s is a form of dementia characterized by extracellular deposits, neurofibrillary tangles, and neuronal loss. The disease is neurodegenerative, it damages acetylcholine-generating cells in the basal brain. Subsequently, a major reduction of acetylcholine and cholinergic tone is caused, which results in memory impairments. Reduced expression of nicotinic acetylcholine receptors plays a role in dementia pathophysiology associated with the illness. Additionally, deficiency of choline acetyltransferase enzyme in inpatient’s brain also triggers cognitive decline.
Alzheimer’s disease starts in the entorhinal cortex before proceeding to the hippocampus from where it causes the cells to lose connectivity with the neurons and die. As a result, short-term memory wanes, and confusion is experienced. Thereafter, the degeneration of the cerebral cortex is initiated and an individual may have difficulty in judgment and language cognition. As the condition progresses, patients’ ability to recognize close people such as family members and undertake routine simple tasks such as bathing is lost. Suspiciousness, anxiety, pacing, complete mental loss of functioning, and inability to communicate also characterize the disease.
Cholinergic signaling is affected by Alzheimer’s condition because the cholinergic neurons are lost with the progression of the disease due to excessive formation of extracellular beta-amyloid patches and intracellular neurofibrillary tangles. The neurotic plaques formed to disrupt the cholinergic pathways by obstructing the movement of essential nutrients and enzyme into the axons. Consequently, neurons die due to starvation and the presence of beta-amyloid to cause the disease. Acetylcholine level is directly proportional to cognitive ability, hence, people with Alzheimer’s condition have low levels of it.
GABA in Sedatives and Anxiety Reducing Effects
Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that blocks some impulses generated between brain nerve cells. Its receptors are the majority in the central nervous system, thus, it has several effects on regular functioning and it is mostly associated with relaxation and sedation. Excess GABA causes one to be relaxed, physically slower, sleepy, and have lower energy while insufficient is associated with panic attacks, anxiety, and seizures. Generally, this chemical slows down communication and reaction between nerve cells.
An increase in GABA levels in the brain slows the rate of the neuron’s excitement, this results in dopamine release into the reward center called the nucleus accumbens. This hormone is a mood-elevating neurotransmitter, it is associated with good outcomes because it makes one be euphoric and happy. Alcohol has no effects on neurons chemicals, however, they trigger the same effects because it also attaches to GABA receptors in the brain.
The GABA receptor is a protein channel that enables chloride ions passage into cells, excessive activation of this neurotransmitter plays a role in mediating sedative effects of anesthetic agents and alcohol. This is because they boost GABAA-mediated chloride flow into the neuron cell to increase inhibition. Other molecules such as phosphate groups and proteins kinases that modulate the activity of receptors are also influenced by sedatives, opioids, and alcohol.
GABA receptors are embedded in neuron cell membranes and each has five molecules of protein that gather to form a channel. Attachment of molecules such as GABA or benzodiazepines to the receptor excites it. This then causes the passage to allow the flow of negatively charged ions like chloride into the cell. The ions movement decreases cell excitability and inhibits neuronal activities hence slowing down interneuron communication.
Several drugs such as benzodiazepines, barbiturates, gabapentin, and z-drugs have effects on the activity of GABA. For this reason, there is a need to balance GABA levels by using medications for one to avoid mental health conditions and feel normal. Repeated use of recreational drugs triggers GABA surge and a consequent increase in serotonin and dopamine neurotransmitters that causes intoxication. This later leads to compulsive behaviors such as routine substance abuse and addiction. Alcohol is a GABA receptor agonist, too much alcohol overstimulates GABA pathways to cause alcohol toxicity and overdose. However, continuous alcohol utilization desensitizes receptors; this effect causes a person to be stressed and have anxiety. Withdrawal symptoms such as intense confusion, delirium, hallucinations, and body tremors experienced when a person wants to leave alcohol are attributed to numbed GABA receptors.
Benzodiazepines are sedatives utilized to treat insomnia, anxiety, seizure disorder, and panic attacks. They target GABAA receptors, the drug is abused alongside alcohol and opioids. However, in the detoxification process, it is used for less than two weeks to manage GABA levels. This is because prolonged utilization of this medicine has effects on the brain neurotransmitters and leads to tolerance and physical dependence, which leads to tolerance and addiction.
In conclusion, medicine such as benzodiazepines and sedatives, and alcohol binds to GABA receptors hence affecting its activity. The drugs are utilized to increase GABA levels because they create a feeling of relief, happiness, and relaxation. This is because individuals suffering from depression, anxiety, insomnia, and stress synthesize less GABA naturally. However, overuse drives one into being emotionally dependent on the pills because the brain functioning in regulating GABA is reduced.
Reference
Leaderbrand, K., Chen, H. J., Corcoran, K. A., Guedea, A. L., Jovasevic, V., Wess, J., & Radulovic, J. (2016). Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory. Learning & Memory, 23(11), 631-638. Web.