GABA_B receptor‐mediated presynaptic inhibition reverses inter‐columnar covariability of synaptic actions by intracortical axons in the rat barrel cortex

Abstract

Intracortical axons originating from pyramidal cells in layer 3 of the rat somatosensory cortex are shared between adjacent columns, and receive the presynaptic inhibition that is mediated by the GABA(B) receptor. Synaptic actions by intracortical axons of single layer 3 pyramidal cells covary between the two adjacent columns in response to stimulation of layer 3 of either column. We examined whether GABA(B) receptor-mediated presynaptic inhibition affects the covariability of synaptic actions by intracortical axons between adjacent columns in slice preparations of the rat barrel cortex. Paired stimulations of superficial layer 3 evoked first and second excitatory postsynaptic currents (EPSCs) of varying amplitudes, yielding varying paired-pulse depression of EPSCs in layer 3 pyramidal cells that were located in the stimulated column, but not in its adjacent column. The amplitude of the second EPSC was inversely proportional to that of the first EPSC in layer 3 pyramidal cells in the stimulated column, yielding a negative correlation coefficient between the first and second EPSCs. Baclofen and CGP55845 attenuated paired-pulse depression and abolished the inverse relationship. Simultaneous recordings from two layer 3 pyramidal cells in the stimulated and adjacent columns revealed a positive correlation between the paired first EPSC amplitudes and a negative correlation between the paired second EPSC amplitudes, which, respectively, indicate the positive and negative covariability of synaptic actions by intracortical axons between the two adjacent columns. These results suggest that GABA(B) receptor-mediated presynaptic inhibition can reverse the positive covariability of inter-columnar synaptic actions, which may serve as a basis for inter-columnar desynchronisation.

A mathematical model of negative covariability of inter‐columnar excitatory synaptic actions caused by presynaptic inhibition

“…These assumptions were made based on the following two findings in the electrophysiological experiments. (1) The mean current amplitude in L3 PCs in the AC and that in L5 PCs in the HC were 0.40 and 0.21 times as large as that in L3 PCs in the HC, respectively, in our previous studies (Sato et al ., ). (2) The mean amplitudes of unitary EPSCs in L3 (3.33 pA) and L5 PCs (3.75 pA) were estimated from the mean amplitudes of unitary EPSPs in L3 (0.5 mV) and L5 PCs (0.3 mV) (Reyes & Sakmann, ) and the input resistances of L3 (150 MΩ; Sarid et al ., ; Zilberter et al ., ) and L5 PCs (80 MΩ; Zhu, ).…”

“…(2) The mean amplitudes of unitary EPSCs in L3 (3.33 pA) and L5 PCs (3.75 pA) were estimated from the mean amplitudes of unitary EPSPs in L3 (0.5 mV) and L5 PCs (0.3 mV) (Reyes & Sakmann, ) and the input resistances of L3 (150 MΩ; Sarid et al ., ; Zilberter et al ., ) and L5 PCs (80 MΩ; Zhu, ). Both the N 0 and the N B were set at 29 and B (1 or 2, 0.5) so as to yield the expected value of the N 1st = 29.5 or 30.0 that causes the composite EPSCs with the mean amplitudes of 100 pA in L3 PCs in the HC, which is similar to that observed in our previous study (Sato et al ., ). The expected values of the N 1st with N 0 = 29 and N B ~ B (2, 0.5) in L3 PCs in the AC and that with N 0 = 29 and N B ~ B (1, 0.5) in L5 PCs in the HC were 12.0 and 5.6, respectively.…”

“…However, it remains unknown whether any other inhibitory actions are involved in the slow synchronization. We previously demonstrated that in the rat barrel cortex the GABA B presynaptic inhibition of common excitatory synaptic inputs is involved in the desynchronization of such excitatory synaptic inputs between L3 pyramidal cells (PCs) in mutually adjacent columns (Sato et al ., ). Then, synchronization of firing activities at lower frequencies (< 5 Hz) may occur following the liberation from the GABA B presynaptic inhibition of excitatory synaptic inputs.…”

“…This fluctuation may be partly because synaptic vesicles are randomly and independently released from respective release sites following the binomial distribution (McLachlan, ; Redman, ) and partly due to the spontaneous oscillatory activity (Flint & Connors, ), while the inverse relationship was considered to be due to the back‐and‐forth interplay between excitatory principal neurons and GABAergic interneurons (Traub et al ., ). Simultaneous recordings of the two cells revealed a positive or negative correlation coefficient between the amplitudes of the second EPSCs depending on the location of the two cells either in the same column or in the two adjacent columns (Sato et al ., ).…”

“…Using slice preparations of the rat barrel cortex (Sato et al ., ), we have previously demonstrated that paired‐pulse stimulation of L3 caused the paired‐pulse depression (PPD) of excitatory postsynaptic currents (EPSCs) in L3 PCs via GABA B ‐receptor‐mediated presynaptic inhibition of intracortical inputs. In response to repetitive paired stimulations with a constant intensity, the amplitudes of the first and second EPSCs fluctuated in an inversely correlated manner.…”