The Many Forms and Functions of Long Term Plasticity at GABAergic Synapses

Abstract

On February 12th 1973, Bliss and Lomo submitted their findings on activity-dependent plasticity of glutamatergic synapses. After this groundbreaking discovery, long-term potentiation (LTP) and depression (LTD) gained center stage in the study of learning, memory, and experience-dependent refinement of neural circuits. While LTP and LTD are extensively studied and their relevance to brain function is widely accepted, new experimental and theoretical work recently demonstrates that brain development and function relies on additional forms of plasticity, some of which occur at nonglutamatergic synapses. The strength of GABAergic synapses is modulated by activity, and new functions for inhibitory synaptic plasticity are emerging. Together with excitatory neurons, inhibitory neurons shape the excitability and dynamic range of neural circuits. Thus, the understanding of inhibitory synaptic plasticity is crucial to fully comprehend the physiology of brain circuits. Here, I will review recent findings about plasticity at GABAergic synapses and discuss how it may contribute to circuit function.

Cell Type-Specific, Presynaptic LTP of Inhibitory Synapses on Fast-Spiking GABAergic Neurons in the Mouse Visual Cortex

“…These functions are implemented by inhibitory circuits, including excitatory synapses on GABAergic interneurons. These excitatory synapses on GABAergic interneurons show the spike time-dependent or Hebbian type of LTP, as reported previously (Lamsa et al, 2005;Sarihi et al, 2008, Perez et al, 2001; for review, see Maffei, 2011). This potentiation of inhibitory circuits may last for a long time.…”

“…LTP of GABAergic synaptic transmission has been extensively studied in the visual cortex (Komatsu and Iwakiri, 1993;Komatsu, 1994;Maffei et al, 2006), hippocampus (Grunze et al, 1996;McLean et al, 1996;Caillard et al, 1999;Gubelline et al, 2001;Patenaude et al, 2003), and other regions of the brain (for review, see Maffei, 2011). However, all of these studies, except for the one on brainstem dopamine neurons (Nugent et al, 2007), reported LTP of inhibitory synapses on pyramidal or excitatory principal neurons.…”

“…These inhibitory circuits are thought to play a role in stability of pyramidal cell activity, formation of receptive fields, selectivity of responses, synchronization of neuron activities, and other functions in the adult cortex (Alitto and Dan, 2010;Maffei, 2011;Isaacson and Scanziani, 2011). These functions are implemented by inhibitory circuits, including excitatory synapses on GABAergic interneurons.…”

Neurotransmitters and Memory

“…Certainly, activity-dependent plasticity of glutamatergic synapses, such as LTP and LTD, gained center stage in the study of learning, memory, and experiencedependent refinement of neural circuits (Maffei, 2011). Both LTP and LTD are extensively studied and their relevance to brain function is widely accepted, new experimental and theoretical work recently demonstrates that brain development and function relies on additional forms of plasticity, some of which occur at nonglutamatergic synapses (Maffei, 2011).…”

The Role of Blue Native/ SDS PAGE in Depression Research

“…The expression and modification of synaptic proteins is dynamically regulated, depending on the neuronal activity. This process is called synaptic plasticity, and is thought to be the cellular basis of learning and memory (Bagal et al, 2005;Maffei, 2011;Martin & Morris, 2002). Plasticity-induced changes can occur on both sides of the synapse by altering Ca 2+ -dependent neurotransmitter release from the presynaptic nerve terminal and/or modifying the response to neurotransmitter in the postsynaptic neuron (Evans & Morgan, 2003).…”