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International audience; This special issue is a companion to the meeting 'XVth International Symposium on Cholinergic Mechanisms', and is edited by Israel Silman, Marco Prado and Pascale Marchot. In the review articles, renowned researchers in the field capture key mechanisms of cholinergic neurotransmission, from genomic amplification of cholinesterase genes, splicing and post-translational modifications; features of the neuromuscular junction, implications of cholinergic circuitry that are relevant to addiction, anxiety and mood, to preclinical models, protein biomarkers, and clinical findings that are relevant to pathology, for example, developmental neurotoxicity. The broad variety of features reflects the impact of cholinergic mechanisms on many physiological events and emphasizes the importance of research in this area. This is the Preface for the special issue XVth International Symposium on Cholinergic Mechanisms.

International audience; Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in β-strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three-finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system. By blocking the activity of the nicotinic and muscarinic acetylcholine receptors or by inhibiting the enzyme acetylcholinesterase, three-finger fold toxins interfere most drastically with neuromuscular junction functioning. Several of these toxins have become powerful pharmacological tools for studying the function and structure of their molecular targets. Most importantly, since dysfunction of these receptors/enzyme is involved in many diseases, exploiting the three-finger scaffold to create novel, highly specific therapeutic agents may represent a major future endeavor. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

Acetylcholine (ACh) is known to shape the adult neocortical activity related to behavioral states and processing of sensory information. However, the impact of cholinergic input on the neonatal neuronal activity remains widely unknown. Early during development, the principal activity pattern in the primary visual (V1) cortex is the intermittent self-organized spindle burst oscillation that can be driven by the retinal waves. Here, we assessed the relationship between this early activity pattern and the cholinergic drive by either blocking or augmenting the cholinergic input and investigating the resultant effects on the activity of the rat visual cortex during the first postnatal weekin vivo. Blockade of the muscarinic receptors by intracerebroventricular, intracortical, or supracortical atropine application decreased the occurrence of V1 spindle bursts by 50%, both the retina-independent and the optic nerve-mediated spindle bursts being affected. In contrast, blockade of acetylcholine esterase with physostigmine augmented the occurrence, amplitude, and duration of V1 spindle bursts. Whereas direct stimulation of the cholinergic basal forebrain nuclei increased the occurrence probability of V1 spindle bursts, their chronic immunotoxic lesion using 192 IgG-saporin decreased the occurrence of neonatal V1 oscillatory activity by 87%. Thus, the cholinergic input facilitates the neonatal V1 spindle bursts and may prime the developing cortex to operate specifically on relevant early (retinal waves) and later (visual input) stimuli.