Historical landmarks in the histochemistry of the cholinergic synapse: perspectives for future researches

Abstract

Nearly one hundred years ago, acetylcholine (ACh) was proposed as a chemical agent responsible for nerve transmission at the synapse, the junction area between one neuron and its target cell. Since it has been proved that ACh played, indeed, a major role in the functioning of the nerve system in the vertebrates, cholinergic nerve transmission became a basic field of study in neuroscience. The birth of histochemistry and its ulterior developments allowed in situ localization of the molecular agents related to the functioning of the cholinergic synapse. This report presents historical landmarks in the histochemistry of major cholinergic agents (acetylcholinesterase, nicotinic acetylcholine receptor, choline acetyltransferase, and ACh), a domain which has greatly contributed to the knowledge of the nerve system. It is emphasized that despite extraordinary progresses made in this field, basic problems, such as in situ localization of ACh, still remain to be solved.

Peripheral type of choline acetyltransferase: Biological and evolutionary implications for novel mechanisms in cholinergic system

“…In the peripheral nervous system (PNS), parasympathetic cholinergic neurons are involved in the control of visceral functions (cardiac muscle, vascular smooth muscle and secretory glands) (Raezer et al, 1973;Fields et al, 1978;Ludmer et al, 1986;Verspohl et al, 1990;De Biasi, 2002;Racke et al, 2006;Proctor and Carpenter, 2007) and enteric cholinergic neurons play key roles in the control of gastrointestinal tract functions (Kosterlitz and Lees, 1964;Furness, 2006). So far, there is no available method to visualize ACh in neurons (Anglade and Larabi-Godinot, 2010). Immunohistochemistry for the ACh synthesis enzyme choline acetyltransferase (ChAT) has been considered as the most reliable method to visualize cholinergic structures (Kimura et al, 1980;Eckenstein and Sofroniew, 1983;Arvidsson et al, 1997;Misawa et al, 2001).…”

“…The context of pChAT discovery 2.1. ChAT the best, yet imperfect, marker for cholinergic neurons Although ACh was the first neurotransmitter to be identified (Loewi, 1921), visualization of ACh in cells is still an unsolved technical challenge (Anglade and Larabi-Godinot, 2010). For many decades this lack of method has prevented progress in understanding cholinergic neuroanatomy, but generated considerable research efforts aimed at identifying other markers specific for cholinergic neuron.…”

Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

“…The brains of AD patients show indeed decreased ACh [23] and glucose contents [24]. To increase the ACh amount of AD brains by ACh esterase inhibitors is the most effective therapy of AD at the moment [25]. Decrease of PHP activity could cause not only an increase of ACL activity and consequently ACh content but also an increase of energy metabolism in neuronal cells.…”

Correlative microscopy: A powerful tool for exploring neurological cells and tissues

“…The reliability of histochemical techniques to specifically label certain populations of neurons relies in part on the ability of the target enzyme to be a unique marker. For example, acetylcholinesterase histochemistry stains cholinergic neurons, but it may also label some noncholinergic neurons that contain the enzyme (Eckenstein and Sofroniew, 1983;Vincent, 1992;Anglade and Larabi-Godinot, 2010). Moreover, since the detection system depends on the formation of a precipitate, reactions must be monitored to prevent over-production of reaction product and methods optimized to prevent diffusion of the reaction product from the site of enzyme activity.…”