Fig. 6. LRIPs enhance CA1 pyramidal neuron dendritic depolarization in response to SC stimulation through disinhibition.

A. Experimental scheme for assessing the synaptic response in CA1 PN dendrites to paired EC-SC electrical stimulation. Panel shows approximate locations of EC and SC stimulation electrodes and dendritic recording pipette. B. Dendritic voltage responses to paired EC-SC electrical stimulation at indicated delays (SC after EC), in absence (left) or presence (right) of SR95531 (2 µM) and CGP55845 (1 µM). Grey dashed line, amplitude of PSP evoked by SC stimulation alone. Red dashed line, predicted linear sum of PSPs evoked by EC and SC stimulation alone. C. Summary plot (mean ± SEM) of paired EC-SC peak PSP normalized by PSP evoked by SC stimulation alone recorded in CA1 PN proximal dendrites in absence (blue squares) and presence (red circles) of GABAR blockers (EC-SC −20 ms pairing: with inhibition intact, fold change = 1.35 ± 0.02; with inhibition blocked, fold change = 1.08 ± 0.03; P = 0.001, Two way ANOVA with Sidak multiple comparisons test, n = 5). D. Experimental scheme to determine how silencing LRIPs (denoted by X) affects PSP in CA1 PN distal dendrites during paired EC-SC stimulation. PSAM expressed in LEC GABAergic neurons in GAD2-Cre mouse with AAV^Cre. E. CA1 PN distal dendrite PSPs evoked by paired stimulation of EC-SC inputs at indicated intervals, first in absence (left) and then in presence (right) of PSEM. F. Mean (± SEM) PSP amplitude recorded in CA1 PN distal dendrites evoked by paired EC-SC stimulation normalized by PSP evoked by SC stimulation alone, in absence (blue squares) and presence (red dots) of PSEM. PSEM significantly reduced the effect of paired EC-SC stimulation at −20 ms delay to increase PSP size (Control, 1.45 ± 0.07 fold increase; PSEM, 1.04 ± 0.07 fold increase; P < 0.001, Two way ANOVA with Sidak multiple comparisons test, n = 8).