Cholinergic interneuron characteristics and nicotinic properties in the striatum

Abstract

ABSTRACT:The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

Nicotinic receptors as CNS targets for Parkinson's disease

“…These include the GABAergic medium spiny projection neurons that comprise the greater majority (~95%) of neurons, as well as a much smaller population of interneurons (5%) of which the majority are GABAergic and about a third cholinergic. These larger cholinergic interneurons form a dense network in striatum that closely overlaps with dopaminergic terminals [10]. Thus high levels of acetylcholine, choline acetyltransferase and acetylcholinesterase [59] coincide with expression of dopamine, tyrosine hydroxylase and other dopaminergic markers [60].…”

“…Thus high levels of acetylcholine, choline acetyltransferase and acetylcholinesterase [59] coincide with expression of dopamine, tyrosine hydroxylase and other dopaminergic markers [60]. Under physiological conditions, the cholinergic interneurons are tonically active [10]. They release acetylcholine, which subsequently interacts with nAChRs on striatal cell bodies and nerve terminals, including dopaminergic projections from the substantia nigra and glutamatergic afferents from the cortex [61][62][63][64].…”

“…This review focuses on the involvement of the nicotinic cholinergic system in Parkinson's disease for the following reasons. First, its close association and functional interaction with the nigrostriatal dopaminergic system suggests that nicotine or nicotinic agonists have potential in treatment of the motor symptoms of the disease [10,11]. In addition, the finding that stimulation of the nicotinic cholinergic system ameliorates cognitive declines [12] suggests that nicotinic acetylcholine receptor (nAChR) drugs may be useful in treating some of the nondopaminergic deficits associated with Parkinson's disease, such as dementia that develops in 50% of Parkinson's disease patients with disease progression [1][2][3][4].…”

The Role of Acetylcholine in Cocaine Addiction

“…ACh interneurons are the primary source of ACh to the dorsal and ventral striatum (Calabresi et al, 2000;Pisani et al, 2001;Zhou et al, 2002). These interneurons integrate a variety of cognitive, limbic, and motor information (Tisch et al, 2004) and undergo plasticity and learning, which, in turn, influences striatal output signaling (Aosaki et al, 1994).…”

Comorbidité entre la dépression et l’addiction

“…Les 5 % de neurones du NAc restants sont constitués d'interneurones dont les neurones cholinergiques (1 % des neurones) représentent la seule source d'acétylcholine pour cette structure [12]. Les neurones du NAc se différencient par leur signature moléculaire, mais aussi par leurs contributions aux réponses adaptatives induites par les drogues.…”