Related Experiment Video
Updated: Jul 14, 2026
14:37
Whole-cell Patch-clamp Recordings from Morphologically- and Neurochemically-identified Hippocampal Interneurons
Published on: September 30, 2014
Functional characterization of intrinsic cholinergic interneurons in the cortex.
Jakob von Engelhardt1, Marina Eliava, Axel H Meyer
1Department Clinical Neurobiology, University of Heidelberg, 69120 Heidelberg, Germany.
Summary
Researchers identified intrinsic cholinergic interneurons in the cortex. These neurons modulate cortical function indirectly by increasing excitatory postsynaptic currents in pyramidal neurons via nicotinic receptors.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Cortical Circuitry
Background:
- Acetylcholine is a key neurotransmitter regulating cortical functions.
- Cholinergic input to the cortex originates from basal forebrain neurons and intrinsic interneurons.
- The functional role of intrinsic cholinergic interneurons in cortical microcircuits remains largely unknown due to their low numbers.
Purpose of the Study:
- To functionally characterize intrinsic cholinergic interneurons in the cortex.
- To overcome limitations in studying these cells due to their paucity.
- To investigate the microcircuit interactions and modulatory effects of these neurons.
Main Methods:
- Generation of transgenic mice expressing enhanced green fluorescent protein (EGFP) in choline acetyltransferase (ChAT)-positive neurons.
- Electrophysiological characterization including paired recordings.
- Immunohistochemical analysis for cell morphology and marker expression (calretinin, vasoactive intestinal peptide).
Main Results:
- Identified distinct cholinergic interneurons in layer 2-3 with bipolar morphology, expressing calretinin and vasoactive intestinal peptide, and lacking a GABAergic phenotype.
- Demonstrated that EGFP/ChAT-positive neurons receive excitatory and inhibitory inputs from adjacent cells.
- Showed that these neurons do not directly elicit postsynaptic responses but indirectly increase spontaneous EPSCs in pyramidal neurons via presynaptic nicotinic receptors.
Conclusions:
- Intrinsic bipolar cholinergic neurons represent a distinct interneuron population in the cortex.
- These neurons can locally modulate cortical activity through indirect mechanisms.
- The findings highlight a novel pathway for cholinergic modulation within cortical microcircuits.
Related Concept Videos
01:23Cholinergic Neurons: Neurotransmission
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
01:25Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
01:15Cholinergic Receptors: Nicotinic
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
01:22Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
The direct-acting...
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...