Theory of optimal balance predicts and explains the amplitude and decay time of synaptic inhibition

Abstract

Synaptic inhibition counterbalances excitation, but it is not known what constitutes optimal inhibition. We previously proposed that perfect balance is achieved when the peak of an excitatory postsynaptic potential (EPSP) is exactly at spike threshold, so that the slightest variation in excitation determines whether a spike is generated. Using simulations, we show that the optimal inhibitory postsynaptic conductance (IPSG) increases in amplitude and decay rate as synaptic excitation increases from 1 to 800 Hz. As further proposed by theory, we show that optimal IPSG parameters can be learned through anti-Hebbian rules. Finally, we compare our theoretical optima to published experimental data from 21 types of neurons, in which rates of synaptic excitation and IPSG decay times vary by factors of about 100 (5-600 Hz) and 50 (1-50 ms), respectively. From an infinite range of possible decay times, theory predicted experimental decay times within less than a factor of 2. Across a distinct set of 15 types of neuron recorded in vivo, theory predicted the amplitude of synaptic inhibition within a factor of 1.7. Thus, the theory can explain biophysical quantities from first principles.

Recovery of consolidation after sleep following stroke—interaction of slow waves, spindles, and GABA

“…What might be the underlying neurophysiological basis for our observed changes in SO and d I waves with recovery? One possibility is that elevations in extra-synaptic g-aminobutyric acid (GABA) after stroke exp may alter local excitability and thus perturb the ability of global SOs to organize local d. Studies have reported that reducing such tonic inhibition can have a beneficial effect on recovery (Clarkson et al, 2010;He et al, 2019), implying that altered excitation-inhibition (E-I) balance (Kim and Fiorillo, 2017;Xia et al, 2017;Yizhar et al, 2011) plays a role in recovery.…”

The Objective Bayesian Probability that an Unknown Positive Real Variable Is Greater Than a Known Is 1/2

“…Probabilities are typically used to describe the knowledge of scientists, but they can also be used to describe the information in a cognitive or physical model of an observer. This is the basis of Bayesian accounts of biology and psychology that view an organism as a collection of observers that predict and cause the future [21,[30][31][32][33][34][35][36][37][38][39][40].…”

“…However, we do not think it is overly simplistic for a model of a physical observer to be just a single quantity at a single moment in time. The brain is a multitude of local physical observers, but our initial concern is just a single observer at a single moment [21,22,[33][34][35]. The problem is greatly simplified by the fact that we equate an observer with information, and information with a physical quantity that is local in space and time, and is described by a single number.…”

Recovery of consolidation after sleep following experimental stroke – interaction of slow waves, spindles and GABA

“…Studies have reported that elevated GABAA-mediated tonic inhibition reduces network excitability, and that reducing such inhibition can have a beneficial effect on recovery (Clarkson et al, 2010;He et al, 2019). These studies specifically imply that an altered excitation-inhibition balance (Kim and Fiorillo, 2017;Xia et al, 2017;Yizhar et al, 2011) plays an important role in motor recovery. Thus, we tested the effects of blocking GABAA-mediated tonic inhibition after stroke on the temporal coupling of spindles to slow-waves.…”