Cholinergic neuron

A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. Many neurological systems are cholinergic. Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep. The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease. The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease. A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. Many neurological systems are cholinergic. Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep. The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease. The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease. Most research involving cholinergic neurons involves the basal forebrain cholinergic neurons. However, cholinergic neurons only represent about 5% of the total basal forebrain cell population. Most of these neurons originate in different areas of the basal forebrain and have extensive projections into almost all layers of the cortex. Basal forebrain cholinergic neurons are homologous within a particular basal forebrain region but vary across different regions. In the brainstem acetylcholine originates from the pedunculopontine nucleus and laterodorsal tegmental nucleus collectively known as the meso-pontine tegmental area or pontomesencephalotegmental complex. Normal aging is described as aging unaccompanied by the behavioral or cognitive dysfunctions associated with the cholinergic basal forebrain system. In normal aging, there are beadlike swellings within the cholinergic fibers with enlarged or thickened axons, often in grape-like clusters. This fiber swelling can be induced in a laboratory setting by damaging the cell body of the cholinergic neuron, which implies there is a slow cell and fiber degeneration of affected neurons and their projecting axons. Nerve growth factor protects cholinergic neurons. The small non-toxic molecule urea has no neuroprotective effect on cholinergic neurons by itself, but when experimental brain slices were treated with nerve growth factor and urea, the number of cholinergic neurons in the brain slices was significantly enhanced when compared to slices treated with nerve growth factor only. The enhancing effect of urea may be due to inhibition of the nitric oxide-system within the cholinergic neuron. Cholinergic neurons, along with non-cholinergic neurons, have sleep/wake regulatory functions in the basal forebrain that can be categorized based on their firing patterns in different regions. The cholinergic system allows the circadian system to have the cycle of one day. The cholinergic neuron may also play a role in time memory, and the ability of an individual to form a memory around a certain time of day, which is known as 'time stamping'. The cholinergic system is characterized by high acetylcholine release during the active phase of an individual’s circadian rhythm. In the medial septum-diagonal band of Broca's area of the brain, cholinergic neurons have very low firing rates during both wake and non-REM sleep, and show no rhythmic bursts during hippocampal (theta) Electroencephalography activity. However, cholinergic neurons in the magnocellular preoptic nucleus and Substantia innominata have increased firing rates with fast cortical (gamma) Electroencephalography activity during wake and rapid eye movement sleep. This indicates that cholinergic neurons may be activated through α1-receptors by noradrenaline, which were released by locus coeruleus neurons during wake cycles. In a basic summary, cholinergic neurons are always active during wake or rapid eye movement sleep cycles, and are more likely to activate the cerebral cortex to induce the gamma wave and Theta rhythm activities while behaviorally promoting the states of wakefulness and rapid eye movement sleep. The suprachiasmatic nucleus functions as the hypothalamic master clock, controlling the body's Circadian rhythm. The suprachiamatic nucleus of mice, hamsters, and rats have a small amount of cholinergic innervation. A 'time memory' is the memory at a specific time of day for which an individual made an association with a certain event or location. 'Time stamping' is the process by which the specific time-of-day is encoded to support the formation of a time memory. The situation must be important and specific, without unnecessary prolonging, for a time stamp to occur. Acetylcholine excites cells in the suprachiasmatic nucleus, so cholinergic transmission of more Acetylcholine into the suprachiasmatic nucleus should support the formation of a time memory. The number of free and available muscarinic acetylcholine receptors (mAChRs) is highest when acetylcholine release is at the lowest levels. When a memorable event occurs, there is a massive release of acetylcholine that will attach to mAChRs. Once too many are involved, the mAChRs will reduce or block further cholinergic input, which protects these cells and the networks from additional cholinergic input that could disrupt the signal. This allows the suprachiasmatic nucleus to perform time stamping and produce a time memory of what has just occurred to the individual. If correct, this would explain the cholinergic neuron’s role in memory. The circadian system is one of the first systems to be damaged in Alzheimer's disease. Alzheimer's patients often complain of disrupted sleep, shortened rapid eye movement sleep, and increased night time awakening. These disruptions steadily worsen as the disease progresses. It is normal in aging for circadian rhythms to deteriorate as choline acetyltransferase (ChAT) fluctuations change in pattern and acetylcholine levels fluctuate more often. As Alzheimer's disease drastically changes cholinergic function, the circadian system naturally follows the changed levels. Circadian rhythmicity in acetylcholine release is critical for optimal memory processing, and a loss of this rhythmicity contributes to cognitive problems in Alzheimer's disease.