Plasticity of cortical excitatory-inhibitory balance

Abstract

Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

Keywords: cortex; inhibition; neuromodulation; synaptic plasticity.

Figure 1

STDP of excitatory (a) and inhibitory (b) synaptic responses recorded in the same cells from slices of young mouse auditory cortex. (Top and middle) Examples of LTP and LTD induced by spike pairings of various timing intervals. Blue symbols in panel b indicate experiments performed with excitation blocked via DNQX. (Bottom) Summary of all cells, showing that spike pairing differentially affects excitation versus inhibition. Excitatory STDP has a Hebbian asymmetric window [short-interval pre-before-postsynaptic pairing (pre→post pairing) induced LTP, and post→pre pairing induced LTD], whereas inhibitory STDP is symmetric (LTP is induced by both pre→post and post→pre pairings). Adapted from D’amour & Froemke (2015). Abbreviations: ACSF, artificial cerebrospinal fluid; DNQX, 6,7-dinitroquinoxaline-2,3-dione; LTD, long-term depression; LTP, long-term potentiation; pA, picoamperes; STDP, spike timing–dependent plasticity.

Figure 2

Development of cortical excitatory-inhibitory balance. (a) Balanced tone-evoked excitation and inhibition in adult rat primary auditory cortex. (Top) Frequency tuning curves for excitatory and inhibitory conductances. (Bottom) Excitation and inhibition were highly correlated (linear correlation coefficient r = 0.87). (b) Imbalanced excitatory and inhibitory frequency tuning in auditory cortex early in development. Whole-cell recording from a young [postnatal day 14 (P14)] rat (r = −0.01). Adapted from Dorrn et al. (2010). Abbreviation: nS, sanosiemens.

Figure 3

Functional consequences of nucleus basalis pairing. (a) Experimental setup for electrophysiological studies. (b) Synaptic tuning curve before pairing. Note cotuning of excitatory and inhibitory tuning curves. The triangle indicates the original best frequency, and the arrow indicates the frequency to be paired with nucleus basalis stimulation. (c) The same cells as in panel b 30 min after pairing. Inhibitory responses at the paired 4 kHz input have decreased, and the excitatory tuning curve has shifted to have a new peak at 4 kHz. (d) A different cell from the same animal as in panels b and c 180 min after pairing. Excitatory-inhibitory balance has recovered, but the tuning preference for both excitation and inhibition has shifted from the original best frequency (16 kHz) to the paired frequency (4 kHz). (e) Nucleus basalis pairing improves auditory perception. (Left) Diagram of behavioral training setup. (Right) Frequency recognition (top) and detection (bottom) of a paired 4 kHz tone before and 1–2 h after nucleus basalis pairing. Hit rates (circles) were enhanced to paired target tones, whereas false alarms (triangles) were unaffected. Adapted from Froemke et al. (2007, . Abbreviations: dB SPL, decibels sound pressure level; EPSC, excitatory postsynaptic current; IPSC, inhibitory postsynaptic current.