No abstract

SummaryRepresentations of the external world in sensory cortices may define the identity of a stimulus and should therefore vary little over the life of the organism. In the olfactory system the primary olfactory cortex, piriform, is thought to determine odor identity1–6. We have performed electrophysiological recordings of single units maintained over weeks to examine the stability of odor representations in the mouse piriform cortex. We observed that odor representations drift over time, such that the performance of a linear classifier trained on the first recording day approaches chance levels after 32 days. Daily exposure to the same odorant slows the rate of drift, but when exposure is halted that rate increases once again. Moreover, behavioral salience does not stabilize odor representations. Continuous drift poses the question of the role of piriform in odor identification. This instability may reflect the unstructured connectivity of piriform7–15 and may be a property of other unstructured cortices.

The inner pore of voltage-gated Ca2+ channels (VGCCs) is functionally important, but little is known about the architecture of this region. In K+ channels, this part of the pore is formed by the S6/M2 transmembrane segments from four symmetrically arranged subunits. The Ca2+ channel pore, however, is formed by four asymmetric domains of the same (α1) subunit. Here we investigated the architecture of the inner pore of P/Q-type Ca2+ channels using the substituted-cysteine accessibility method. Many positions in the S6 segments of all four repeats of the α1 subunit (Cav2.1) were modified by internal methanethiosulfonate ethyltrimethylammonium (MTSET). However, the pattern of modification does not fit any known sequence alignment with K+ channels. In IIS6, five consecutive positions showed clear modification, suggesting a likely aqueous crevice and a loose packing between S6 and S5 segments, a notion further supported by the observation that some S5 positions were also accessible to internal MTSET. These results indicate that the inner pore of VGCCs is indeed formed by the S6 segments but is different from that of K+ channels. Interestingly some residues in IIIS6 and IVS6 whose mutations in L-type Ca2+ channels affect the binding of dihydropyridines and phenylalkylamines and are thought to face the pore appeared not to react with internal MTSET. Probing with qBBr, a rigid thiol-reactive agent with a dimension of 12 Å × 10 Å × 6 Å suggests that the inner pore can open to >10 Å. This work provides an impetus for future studies on ion permeation, gating, and drug binding of VGCCs.