Sensory experience can powerfully alter the spatial and temporal organization of population codes in the brain throughout an animal's lifetime. In this dissertation I focus on how changes in sensory experience, by learning or environmental enrichment, alter sensory map topography in rodent primary sensory cortex.
In Chapter 1 I review recent advances in our understanding of how perceptual learning and related sensory manipulations shape the structure of primary sensory cortex maps across multiple sensory modalities. Classic studies of map plasticity in primary sensory cortex have shown that experience shapes sensory tuning in individual neurons and at the average population level. But effective neural population codes depend on more than just sensory tuning in individual cells averaged over time. With population calcium imaging, activity can be measured simultaneously in large ensembles of neurons during behavior. This and related techniques make it possible to study changes in the single-cell level organization of sensory coding, as well as high-dimensional codes that depend on the activity of large ensembles of cells, and which may change with behavioral context. Here I review recent population calcium imaging and recording studies that have characterized population codes in sensory cortex, and tracked how they change with sensory manipulations and training on perceptual learning tasks. These studies confirm average sensory tuning changes observed in earlier studies, but also reveal other features of plasticity, including sensory gain modulation, restructuring of firing correlations, and differential routing of information to output pathways. Unexpectedly strong day-to-day variation exists in single-neuron sensory tuning, which stabilizes during learning. These are novel dimensions of plasticity in sensory cortex, which refine population codes during learning, but whose mechanisms are unknown.
Most of what is known about how sensory experience shapes maps is based on studies that have used robust sensory manipulations, such as deprivation, chronic over-stimulation, or explicit pairing of a sensory stimulus with a reward or punishment, as in the studies discussed in Chapter 1. However, much less is known about how maps are refined by natural behavior-driven sensory experience. To understand how natural tactile experience influences map development, We studied the effects of tactile enrichment on the organization of the whisker map in mouse primary somatosensory cortex (S1), which is highly plastic throughout life and which contains an anatomically well-defined map of the whiskers. Mice were raised with enrichment (EN) or normal housing (CT) beginning at weaning (P21). We focused our study on Layer 2/3 (L2/3), which is particularly plastic and which has a “salt-and-pepper” organization of whisker tuning, and Layer 4 (L4), which contains the anatomical map of the whiskers. The genetically-encoded calcium indicator GCaMP6s was expressed virally in L2/3 or L4 excitatory cells using cell-type and layer-specific Cre mice. At P62 ± 13 days, we measured neuronal responses to 9 whiskers using 2-photon imaging through a chronic cranial window. After imaging was complete, cells were localized relative to anatomical barrel column boundaries corresponding to the whiskers in the stimulus set. Within a single anatomical column in both L2/3 and L4 excitatory cells, cells were heterogeneously tuned to different whiskers. Enrichment increased somatotopic precision (the fraction of cells within a certain radius that were anatomically tuned) in both layers near the centers of anatomical columns. Enrichment also sharpened whisker tuning curves in both layers, and essentially increased signal-to-noise of whisker coding in L2/3 by decreasing spontaneous activity while maintaining response magnitudes for columnar whiskers. In L2/3, point representations (the density and spatial spread of neurons responding to a whisker) were sharpened by increased whisker responses among cells located close to column centers.
To study the impact of enrichment on the spatial and temporal structure of population coding, we compared pairwise noise and signal correlations in whisker-evoked activity within each column. In L2/3, signal correlations – which reflect overall tuning similarity – were similar in EN and CT for pairs within columns, though signal correlations were higher in EN for pairs located further apart. However, for pairs of neurons located across column boundaries but at similar distances, signal correlations were dramatically decreased in EN, while comparable to in-column levels in CT. In both groups, noise correlations – which reflect shared trial-by-trial variability that is independent of the stimulus – decreased sharply with distance between neurons. For pairs of cells across column boundaries in CT mice, signal and noise correlations exhibited the same relationships with inter-cell distance as within column pairs; however, In EN mice, cross-column signal and noise correlations were substantially reduced compared to in-column pairs. Essentially, enrichment induced reorganization of functional correlations along anatomical column boundaries. This suggests that enrichment may selectively alter connectivity and/or shared synaptic input according to column boundaries.
These findings demonstrate a strong impact of juvenile sensory experience on functional columnar topography and organization in S1, and indicate that enrichment sharpens whisker representations at the population level in L2/3.