Developmental Plasticity of Inhibitory Circuitry

Abstract

In 1949, Donald Hebb proposed a mechanism for use-dependent synaptic plasticity, suggesting that input neurons that reliably activate their postsynaptic target will strengthen their connections (Hebb, 1949). Since then, studies of use-dependent plasticity during development have been almost entirely focused on excitatory synapses, particularly those incorporating NMDA receptors (NMDARs). Neural circuits depend heavily on inhibition, however. Although there have been several in vitro studies of possible synaptic mechanisms underlying inhibitory plasticity Alger, 1992, 1994;Komatsu, 1994;Kano, 1995;Zilberter, 2000;Kreitzer and Regehr, 2001;Wilson and Nicoll, 2001;Kilman et al., 2002;Maffei et al., 2006), little is known at the systems level about use-dependent plasticity of inhibitory synapses. The realization that "inhibitory" neurotransmitters often depolarize immature neurons (Ben-Ari, 2002) further complicates the picture. This issue is important because clinical treatments for epilepsy, sensory dysfunction, or brain damage need to be informed by an understanding of both excitatory and inhibitory components of the circuits they are aimed at influencing. This mini-symposium, presented at the 36th Annual Meeting of the Society for Neuroscience, will address the roles and mechanisms of inhibitory synaptic plasticity during development of the mammalian CNS, using primarily in vivo approaches to examine circuit-level plasticity in a wide array of model systems. The goal of the mini-symposium is to bring this important research area into the spotlight and to encourage other investigators to participate in developing a better understanding of this underappreciated issue. Inhibitory plasticity in motor systemsThe transient presence of episodic bursts of spontaneous network activity (SNA) is observed throughout the developing CNS. In the spinal cord, SNA is important for axon guidance, motoneuron survival, neurochemical expression, and joint and muscle development . Despite its importance, the role of SNA in the maturation of spinal connectivity is poorly understood. In the laboratory of Peter Wenner, co-chair of the mini-symposium, postdoctoral fellow Carlos Gonzalez-Islas has been investigating the role of SNA in homeostatic plasticity within the embryonic chick spinal cord. Despite significant developmental challenges to the production of SNA, it is clear that the network is capable of maintaining its activity levels (Chub and O'Donovan, 1998). Wenner and Gonzalez-Islas hypothesized that SNA is maintained through compensatory changes in synaptic strength. To test this hypothesis, they reduced network activity with lidocaine for 2 d in ovo. This increased the strength of both glutamatergic synapses and immature, depolarizing GABAergic synapses (Gonzalez-Islas and Wenner, 2006) and accelerated the modulation of GABAergic synaptic strength normally observed between episodes of SNA. Together, these compensatory responses appeared to increase the excitability of the embryonic spinal cord in an attempt to maintain approp...

Bilateral cochlear ablation in postnatal rat disrupts development of banded pattern of projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus

“…Similar permissive roles for spontaneous-activity in development of neural circuits have been supported by findings in other sensory systems (McLaughlin and O'Leary, 2005; Ruthazer and Cline, 2004). It is likely that mechanisms influencing the development and refinement of neural circuits in the IC are conserved between sensory systems (Pallas et al, 2006). A small but growing body of information describing the expression of pattern forming molecules has addressed the development of the inner ear and the connections between the cochlea and spiral ganglion in mammals (Lee et al, 1996;Bianchi and Gale, 1998;Cramer, 2005).…”

Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness

“…Finally, GABAergic interneurons play a pivotal role in gating sensory thalamocortical feed-forward inputs [ 20 – 22 ], cortico-cortical [ 23 – 25 ], and corticothalamocortical connectivities between visual cortices [ 26 ] which is of prime interest for cross-modal plasticity following an early sensory loss. Further, significant morphological alterations in inhibitory networks are found in animal models of sensory deprivation, early blindness, rewiring, and cross-modal plasticity [ 1 , 27 – 30 ]. Since interneurons play such a significant role in activity-dependent modification of developing sensory circuits, it is thus important to study specific implications of the various GABAergic subpopulations in cross-modal plasticity paradigms.…”

Age‐dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors

“…Synaptic transmission by endogenous neurotransmitters via autoreceptors or heteroreceptors is modulated within neuronal circuits. A growing body of evidence suggests that plasticity of GABAergic synapses is critical during development and aging, and inhibitory plasticity can function to drive a perturbed system toward homeostasis (Pallas et al, 2006). Aging-related changes in brain function, such as memory impairment, may be related to the imbalance of excitatory and inhibitory transmission.…”