Mechanisms underlying rule learning-induced enhancement of excitatory and inhibitory synaptic transmission

Abstract

Saar D, Reuveni I, Barkai E. Mechanisms underlying rule learning-induced enhancement of excitatory and inhibitory synaptic transmission. J Neurophysiol 107: 1222-1229, 2012. First published November 30, 2011 doi:10.1152/jn.00356.2011.-Training rats to perform rapidly and efficiently in an olfactory discrimination task results in robust enhancement of excitatory and inhibitory synaptic connectivity in the rat piriform cortex, which is maintained for days after training. To explore the mechanisms by which such synaptic enhancement occurs, we recorded spontaneous miniature excitatory and inhibitory synaptic events in identified piriform cortex neurons from odor-trained, pseudo-trained, and naive rats. We show that olfactory discrimination learning induces profound enhancement in the averaged amplitude of AMPA receptormediated miniature synaptic events in piriform cortex pyramidal neurons. Such physiological modifications are apparent at least 4 days after learning completion and outlast learning-induced modifications in the number of spines on these neurons. Also, the averaged amplitude of GABA A receptor-mediated miniature inhibitory synaptic events was significantly enhanced following odor discrimination training. For both excitatory and inhibitory transmission, an increase in miniature postsynaptic current amplitude was evident in most of the recorded neurons; however, some neurons showed an exceptionally great increase in the amplitude of miniature events. For both excitatory and inhibitory transmission, the frequency of spontaneous synaptic events was not modified after learning. These results suggest that olfactory discrimination learning-induced enhancement of synaptic transmission in cortical neurons is mediated by postsynaptic modulation of AMPA receptor-dependent currents and balanced by long-lasting modulation of postsynaptic GABA A receptor-mediated currents.

Learning-induced modulation of the GABAB-mediated inhibitory synaptic transmission: mechanisms and functional significance

“…Such enhanced GABA release was not observed in our present and previous (Saar et al 2012) studies. Notably, such enhanced release is attributed to decrease in the small conductance channel-mediated potassium current which affects repetitive spike firing.…”

“…Our laboratory has previously shown that OD learning is accompanied by enhancement in intrinsic neuronal excitability, excitatory synaptic transmission, and GABA A -mediated fast inhibitory synaptic transmission, throughout the piriform cortex pyramidal cell population (Brosh and Barkai 2009;Saar et al 1998Saar et al , 2002Saar et al , 2012. While activity-induced enhancement in GABA A -mediated inhibitory synaptic transmission has been shown in several brain regions of the mammalian brain (Grunze et al 1996;Holmgren and Zilberter 2001;Komatsu and Yoshimura 2000), plasticity of the GABA B -mediated synaptic inhibition has been less studied.…”

“…These findings suggest that the strength of the late synaptic inhibition is redistributed in the piriform cortex neurons after learning in a manner that might particularly increase synaptic inhibition onto a subgroup of neurons. Since GABA A -mediated inhibition is enhanced after OD learning throughout the pyramidal cell population, and mostly in a subgroup of neurons (Saar et al 2012), it is likely that GABA B -mediated inhibition undergoes a similar change.…”

“…This enhancement is mediated by a strong hyperpolarizing shift in the reversal potential of GABA A receptor-mediated inhibitory postsynaptic potentials (IPSPs). OD rule learning also results in enhanced amplitude of spontaneous inhibitory synaptic events in piriform cortex pyramidal neurons (Saar et al 2012). Moreover, while enhanced synaptic inhibition is evident in most of the recorded neurons (Brosh and Barkai 2009;Saar et al 2012), some neurons receive an exceptionally large increase in GABA A -mediated synaptic inhibition (Saar et al 2012).…”

Differential Modifications of Synaptic Weights During Odor Rule Learning: Dynamics of Interaction Between the Piriform Cortex with Lower and Higher Brain Areas

“…Rats trained in a particularly difficult olfactory discrimination (OD) task demonstrate a dramatic increase in their capability to acquire memories of new odors, termed "rule learning," or "learning set" (Saar et al 1998;Slotnick et al 2000). At the cellular level, rule learning results in a global change in the 3 components controlling the intrinsic PC circuit: intrinsic neuronal excitability (Saar et al 1998;Saar and Barkai 2009), excitatory synaptic inputs (Saar et al 1999(Saar et al , 2002(Saar et al , 2012Knafo et al 2001Knafo et al , 2005Cohen et al 2008), and synaptic inhibition (Brosh and Barkai 2009;Saar et al 2012). These modifications have 2 major common traits:…”