Work

Glycine and glycine transport control dendritic excitability and spiking

Year: 2025

Type: article

Abstract: Neuronal dendrites integrate excitatory input. They can perform local computations such as coincidence detection by amplifying synchronized local input and dendritic spiking. Extracellular glycine could be a powerful modulator of such processes through its action as a co-agonist at glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype but also as a ligand of inhibitory glycine receptors (GlyRs). Similarly, glycine transporters (GlyTs), an emerging drug target for psychiatric and other diseases, could control dendritic integration through ambient glycine levels. Both hypotheses were tested at dendrites of CA1 pyramidal cells in acute hippocampal slices by pharmacologically analysing how glycine, GlyTs and GlyRs change the postsynaptic response to local dendritic excitatory input. Using microiontophoretic glutamate application, we found that glycine can indeed significantly increase dendritic excitability and dendritic spiking. We also uncovered that GlyTs are powerful modulators of dendritic spiking, which can limit the impact of glycine sources on CA1 pyramidal cells. Our experiments also revealed that GlyRs can have an opposite, inhibitory effect on the slow dendritic spike component. This directly demonstrates that glycine can dynamically enhance dendritic responsiveness to local input and promote dendritic spiking, while GlyTs and GlyRs have an opposing effect. Together, this makes glycinergic signalling a powerful modulator of the nonlinear integration of synaptic input in CA1 radial oblique dendrites. • Glycine modulates dendritic excitability and spiking in response to excitatory input • By acting on the NMDAR co-agonist site, glycine lowers the spiking threshold • Through inhibitory glycine receptors, glycine can dampen dendritic spikes • Glycine transporters restrict glycine effects and control dendritic integration • Glycine signalling emerges as a key modulator of nonlinear dendritic integration

Source: Progress in Neurobiology

DOI: 10.1016/j.pneurobio.2025.102856

Authors: Kirsten Bohmbach, Vincent Bauer, Christian Henneberger

Institutions: University of Bonn, German Center for Neurodegenerative Diseases

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $5,190

Funder: Deutsche Forschungsgemeinschaft