In human studies the degree of blindness is reported to affect cross-modal plasticity (Lessard et al., 1998
; D'Angiulli and Waraich, 2002
). Therefore, we examined whether different degrees of visual deprivation could independently recruit unimodal and cross-modal synaptic plasticity. To do this, we compared the effects of different modes of visual deprivation (VD)–including DE, binocular enucleation (EN), and bilateral lid suture (LS)–on synaptic function in both V1 and S1 barrel fields (S1BFs). The different modes of VD was chosen on the basis that DE specifically removes visually-driven activity without impacting spontaneous retinal activity, EN removes both, and LS removes only patterned vision but leaves diffuse light response through the eyelids and spontaneous retinal activity intact. VD was initiated in 3-week-old mice, and AMPAR-mediated miniature excitatory postsynaptic currents (mEPSCs) were recorded from L2/3 pyramidal neurons in V1 and S1BF.
Consistent with our previous findings (Goel et al., 2006
), 7-days of DE (7d-DE) respectively increased and decreased mEPSC amplitudes in V1 and S1BF without altering the frequency (). The amplitude changes followed a multiplicative scaling rule (), which preserves the individual differences in synaptic strength despite global scaling (Turrigiano et al., 1998
). A shorter duration of DE (2d-DE) only increased mEPSC amplitudes in V1 without altering S1BF (), suggesting a longer window of activity integration is needed for cross-modal changes. Changes in mEPSC amplitude support postsynaptic modifications of AMPARs. To further examine this, we analyzed well-isolated mEPSCs from each group using a peak-scaled non-stationary fluctuation analysis (pNSFA) (Traynelis et al., 1993
), which deduces the single channel properties from the variance of the decay phase of mEPSCs (). Dark exposure for 7 days (7d-DE) up-regulated the single-channel conductance (γ) in V1, but decreased the number of open channels at peak (N
) in S1BF, without altering the channel open probability (Popen
) (). The changes in V1 support a scenario that DE recruits Ca2+
-permeable AMPARs (CP-AMPARs) (Goel et al., 2006
; Goel et al., 2011
), which have higher conductance (Swanson et al., 1997
), to replace existing synaptic AMPARs. In S1BF, the decrease in N
suggests that DE reduces the total number of synaptic AMPARs. We found clear differences in basal mEPSC amplitude and larger γ in S1BF than in V1 (), which may reflect more CP-AMPARs at synapses under basal conditions (Goel et al., 2006
). These results support the idea that distinct primary cortical areas have different set points in excitatory synaptic transmission under normal conditions.
Cross-modal regulation of AMPAR-medicated synaptic transmission in S1BF requires a longer duration of visual deprivation than unimodal changes in V1
Binocular enucleation (EN) mirrored the changes seen with DE in both V1 and S1BF (). In contrast, LS did not alter the mean amplitude of mEPSCs in V1 (), suggesting that the residual vision through the eyelids is sufficient to prevent V1 scaling. Seven days of bilateral lid suture (7d-LS) still decreased the amplitude of mEPSCs in S1BF () indicating that cross-modal plasticity is independent of changes in V1. Furthermore, these results suggest that losing patterned vision, which is critical for providing meaningful information for guiding behavior, is sufficient to trigger cross-modal plasticity in S1BF. On the other hand, unimodal changes in V1 require a complete loss of vision. The cross-modal decrease in mEPSC amplitudes with EN and LS followed the rules of multiplicative synaptic scaling like DE ( and ), but only EN mimicked the changes in AMPAR channel function ().
Eliminating spontaneous retinal activity does not add to losing vision
A loss of patterned vision drives cross-modal plasticity of S1BF synapses dependent on whisker inputs
Our results thus far suggest that unimodal changes in V1 are not required to drive cross-modal synaptic changes in S1BF. Therefore, we determined whether cross-modal changes depend on bottom-up sensory information from the whiskers by plucking all whiskers bilaterally during the 7d-LS. Whisker deprivation (WD) alone for 7d did not alter mEPSCs in S1BF, but prevented the amplitude decrease seen with 7d-LS (). Interestingly, 7d-WD cross-modally increased mEPSC amplitudes in V1 () in a non-multiplicative manner (Kolmogorov-Smirnov test between cumulative probability of mEPSC amplitudes of NR scaled by a factor of 1.2 to those of WD: p < 0.001). The direction of cross-modal change in mEPSCs with WD was in the opposite direction to that elicited in S1BF with VD ( and ), which reflects possible opposite subthreshold cross-modal interaction between these two cortical areas (Iurilli et al., 2012
). In any case, the data from S1BF indicate that whisker inputs are necessary for VD-induced cross-modal synaptic plasticity. However, this was not likely due to an increase in whisking activity, because there was no difference in the whisking frequency (both passive and active whisking) between LS and NR (). However, we cannot rule out whether other parameters of whisking, including amplitude, velocity, or duration (Carvell and Simons, 1990
), might be altered. There was no significant change in the general locomotion activity of LS mice measured in their home cages (), which suggests that there is no gross alteration in normal activity.