An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization

Abstract

The organization of sensory maps in the cerebral cortex depends on experience, which drives homeostatic and long-term synaptic plasticity of cortico-cortical circuits. In the mouse primary somatosensory cortex (S1) afferents from the higher-order, posterior medial thalamic nucleus (POm) gate synaptic plasticity in layer (L) 2/3 pyramidal neurons via disinhibition and the production of dendritic plateau potentials. Here we address whether these thalamocortically mediated responses play a role in whisker map plasticity in S1. We find that trimming all but two whiskers causes a partial fusion of the representations of the two spared whiskers, concomitantly with an increase in the occurrence of POm-driven N-methyl-D-aspartate receptor-dependent plateau potentials. Blocking the plateau potentials restores the archetypical organization of the sensory map. Our results reveal a mechanism for experience-dependent cortical map plasticity in which higher-order thalamocortically mediated plateau potentials facilitate the fusion of normally segregated cortical representations.

Keywords: barrel cortex; dendritic signaling; posterior medial complex of the thalamus; somatosensory; synaptic plasticity.

Fig. 1.

IOS detects DWE-evoked plasticity of whisker representation in S1. (A) Schematic of whisker trimming and IOS recording. (B, Left) Examples of averaged baseline and stimulus-related raw IOS evoked by one train of whisker deflections. (Middle) unfiltered and low-pass-filtered t-value maps computed from 20 stimulations. Only pixels with a t-value lower than −2 are included in the responding area (red dashed line). (Right) Whisker C1 (blue) and C2 (red) responding areas. WRD: Euclidian distance between the peaks of the C1 and C2 response areas. (C) Median (± interquartile range) WRD as a function of deprivation duration (in days). (D, Left) Cumulative distribution of WRD in control mice (FWE) and upon DWE. (Right) Median (± interquartile range) WRD. Number of recorded mice is indicated below. *P < 0.05; **P < 0.01; ***P < 0.001.

Fig. 2.

DWE increases plateau potential probabilities. (A) Schematic of recordings in L2/3 cells in vivo in the C2 barrel-related column after >2 d of DWE. (B) Single-cell examples of principal (C2) whisker-evoked responses (gray, single trial traces; dark, averaged trace). Square pulse lines, C2 whisker deflection (100 ms). (C) For each trial, the relationship between the PSP half-peak amplitude and the average membrane potential between 50 and 100 ms after the onset reveals two distinct clusters. Dashed line represents the identity line. (D) Cluster 1 is defined by an index <0 and consists of PSPs containing only a short-latency component that quickly returns to the resting membrane potential. Cluster 2 is defined by an index >0 and consists of compound PSPs with both short- and long-latency components. The long-latency component of the PSP depends on NMDAR (36). For each cell, the NMDAR-plateau potential (Bottom) is derived by subtracting the mean cluster 1 response from the mean cluster 2 response. The integral of the plateau potential is measured from 0 to 300 ms (gray box). (E) Median (± interquartile range) plateau potential probability. (F, Left) Plateau potential grand average (all recorded cells averaged) ± SEM, evoked by the PW (Top) and SW (Bottom) in control mice (dotted line, FWE) and upon DWE (solid line). Square pulse lines, whisker deflection (100 ms). (Right) Median (± interquartile range) plateau potential integral. (G) Mean (± interquartile range) long-latency spike probability (normalized to the spiking probability measured in control mice upon PW stimulation). For E–G, PW and SW correspond to C2 and C1 whiskers, respectively.

Fig. 3.

DWE increases the probability of POm-dependent, NMDAR-mediated plateau potentials. (A) Schematic of the thalamo-cortical circuit and pharmacological experiments. Fluorescent muscimol (0.5 mM) is injected locally in the POm (“musci. in POm”) or in structures not directly involved in somatosensation (“musci. out POm”) for controls. The GABA-A receptor antagonist picrotoxin (iPTX, 1 mM) or the NMDAR open-channel blocker MK-801 (iMK801, 1 mM) are applied directly to the intracellular recording solution. (B) Single-cell example of whisker-evoked responses in different conditions. Gray lines, individual trials; black lines, averaged traces. Square pulse lines: C2 whisker deflection (100 ms). (C) Mean (±SEM) plateau potential probability after DWE. Circles, individual cells. (D) Mean (±SEM) plateau potentials in FWE and DWE mice under different pharmacological conditions. Square pulse lines: C2 whisker deflection (100 ms). (E) Grand average of all extracted PW-evoked plateau potential traces (±SEM) in FWE and DWE mice under various pharmacological conditions. Note that, before averaging cells, the mean plateau potential for each cell was multiplied by its probability of occurrence to compute a trace representing the plateau strength (see SI Appendix, Fig. S1C for details). (F) Mean (±SEM) plateau potential strength in control (FWE) and after DWE under various pharmacological conditions, normalized to the mean measured in FWE mice (dashed line). *P < 0.05; **P < 0.01; ***P < 0.001. ns, not significant.

Fig. 4.

Blocking NMDAR-mediated plateau potentials restores the IOS map. (A, Left) Grand average of all extracted PW-evoked plateau potential traces (±SEM) in FWE and DWE mice. Note that, before averaging cells, the mean plateau potential for each cell was multiplied by its probability of occurrence to compute a trace representing the plateau strength. (Right) Median (± interquartile range) plateau potential strength. (B) Same presentation as in A but for SW-evoked plateau strength. (C) Relation between WRD and PW (black) and SW (gray) plateau strength. Circles: individual cells; squares: averages. (Inset) Median (± interquartile range) plateau potential strength for WRD < λ, in control naive mice (white) and after DWE (black, PW; gray, SW). (D) Schematic of experimental protocol with an example of the IOS in a DWE mouse before and after application of dAP5. Scale bar, 500 µm. (E) Mean (±SEM) WRD in FWE mice (white bars) after DWE (black bars) under different pharmacological conditions (±: before/after drug application, respectively). (F) ΔWRD in FWE mice (white bar) and DWE mice (black bars) following saline or dAP5 application. Blocking NMDAR conductance with dAP5 significantly increases the WRD only in DWE mice. *P < 0.05; **P < 0.01.