Long-term inhibitory plasticity in visual cortical layer 4 switches sign at the opening of the critical period

Abstract

Sensory microcircuits are refined by experience during windows of heightened plasticity termed "critical periods" (CPs). In visual cortex the effects of visual deprivation change dramatically at the transition from the pre-CP to the CP, but the cellular plasticity mechanisms that underlie this change are poorly understood. Here we show that plasticity at unitary connections between GABAergic Fast Spiking (FS) cells and Star Pyramidal (SP) neurons within layer 4 flips sign at the transition between the pre-CP and the CP. During the pre-CP, coupling FS firing with SP depolarization induces long-term depression of inhibition at this synapse, whereas the same protocol induces long-term potentiation of inhibition at the opening of the CP. Despite being of opposite sign, both forms of plasticity share expression characteristics--a change in coefficient of variation with no change in paired-pulse ratio--and depend on GABAB receptor signaling. Finally, we show that the reciprocal SP → FS synapse also acquires the ability to undergo long-term potentiation at the pre-CP to CP transition. Thus, at the opening of the CP, there are coordinated changes in plasticity that allow specific patterns of activity within layer 4 to potentiate feedback inhibition by boosting the strength of FS ↔ SP connections.

Keywords: FS cell; LTD; LTP.

Fig. 1.

Development of unitary FS→SP connection properties. (A) Diagram of the experimental scheme. (B) Average uIPSC at P15–P17 (black) and P21–P23 (gray). (C) Plots summarizing the baseline amplitude, CV, and PPR for connections recorded at P15–P17 (black), P18–P20 (white), and P21–P23 (gray). (D) Peak-scaled average uIPSCs at P15–P17 (black) and P21–P23 (gray) to illustrate change in kinetics. (E) Plots of kinetic parameters for the three groups [P15–P17 (black), P18–P20 (white), and P21–P23 (gray)]. *P < 0.01.

Fig. 2.

The GABA_AR modulator zolpidem has both presynaptic and postsynaptic effects on unitary FS→SP synapses. (A and B) Average uIPSCs recorded in ACSF and ACSF + zolpidem at P15–P16 (A) and P21–23 (B). (C) Effects of zolpidem wash-in on uIPSC decay and (D) PPR, at the two ages [ACSF (black) and ACSF + zolpidem (white); closed circles are means]. (E and F) Plots of the normalized 1/CV² versus normalized mean IPSC amplitude for the two ages. Lines to open circles represent change for individual pairs after zolpidem wash-in, and filled circles represent the averages for each age. **P < 0.01.

Fig. 3.

The sign of plasticity induced by pairing FS and SP activity is developmentally regulated. (A) Example showing effects of pairing FS firing with SP depolarization at P16 on uIPSCs (black, preinduction; gray, postinduction) and the timeline of the change in uIPSC amplitude (Right); here and in subsequent figures, arrow marks time of pairing. (B) Example showing effects of pairing FS firing with SP depolarization at P23 on uIPSCs (black, preinduction; gray, postinduction) and the timeline of the change in IPSC amplitude (Right). (C) Average time course of change in uIPSC amplitude after induction for P15–P17 (black circles), P18–P20 (gray diamonds), and P21–P23 (black triangles). (D) Degree of plasticity at P15–P17 (black), P18–P20 (white), and P21–P23 (gray). Bars and filled circles are average, and open circles are individual pairs. **P < 0.01.

Fig. 4.

Both LTDi and LTPi are dependent on GABA_BR activation. (A) Average uIPSC traces obtained from baseline (black) and postinduction (gray) in presence of 2 µM CGP52432 at P16–P17. (B) (Left) uIPSC amplitude before and after induction in the presence of CGP52432 at P16–P17 (n = 8), (Center) magnitude of change for control (black) and CGP52432 (gray) following induction, and (Right) CV and PPR for both conditions following induction and normalized to baseline. (C) uIPSC amplitude before and after induction in the presence of 2 µm CGP52432 at P22–P23. (D) Same as for B but for induction at P21–23. *P < 0.05; **P < 0.01.

Fig. 5.

Plasticity at reciprocal SP→FS synapses. (A) (Left) Representative scheme of the experimental condition. (Center) Example of the plasticity (and the lack thereof) at a reciprocal FS↔SP connection at P16 (black, preinduction; gray, postinduction). (Right) Example of LTPi obtained at a reciprocal FS↔SP connection at P23 (black, preinduction; gray, postinduction). (B) Plasticity at SP→FS synapses. (Left) Average unitary excitatory postsynaptic current (uEPSC) traces obtained from preinduction (black) and postinduction (gray) at P15–P16, (Center) average uEPSC traces obtained from preinduction (black) and postinduction (gray) at P22–P23, and (Right) average uEPSC traces obtained from preinduction (black) and postinduction (gray) at P22–23 in the presence of 2 µm CGP52432. (C) Degree of plasticity and change in CV at SP→FS connections at P15–P16 (black), P22–P23 (gray), and P22–P23 + CGP52432 (white). *P < 0.05.