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Feldman, D. E.

Publications and source records attributed to Feldman, D. E..

3 recordsLinked to original sources

Tactile enrichment drives emergence of functional columns and improves sensory coding in L2/3 of mouse S1

Sensory maps in layer (L) 2/3 of rodent cortex lack precise functional column boundaries, and instead exhibit locally heterogeneous tuning superimposed on smooth global topography. Could this organization be a byproduct of impoverished experience in laboratory housing? We compared whisker map somatotopy in L2/3 and L4 excitatory cells of somatosensory (S1) cortex in normally housed vs. tactile-enriched mice, using GCaMP6s imaging. Normally housed mice had a dispersed, salt-and-pepper whisker map in L2/3, but L4 was more topographically precise. Enrichment (P21 to P46-71) sharpened whisker tuning and decreased, but did not abolish, local tuning heterogeneity. In L2/3, enrichment strengthened and sharpened whisker point representations, and created functional boundaries of tuning similarity and noise correlations at column edges. Thus, tactile experience drives emergence of functional columnar topography in S1, and reduces salt-and-pepper tuning heterogeneity. These changes predict improved single-trial population coding of whisker deflections within each column.

neuroscience

A normalized template matching method for improving spike detection in extracellular voltage recordings

Spike sorting is the process of detecting and clustering action potential waveforms from extracellular voltage recordings to identify spikes of putative single neurons. Typically, spike detection is done using a fixed voltage threshold and shadow period, but this approach can lead to missed spikes during high firing rate epochs or noisy conditions. We developed a novel spike detection method utilizing a computationally simple form of template matching that efficiently detects spikes from candidate single units and is tolerant of high firing rates and electrical noise without a whitening filter. Template matching was based on a sliding cosine similarity between mean spike waveforms of candidate single units and the extracellular voltage signal. Performance was tested in whisker somatosensory cortex (S1) of anesthetized mice in vivo. The method consistently detected whisker-evoked spikes that were missed by a standard fixed voltage threshold. Detection was most improved for spikes evoked by strong stimuli (40-70% increase), less improved for weaker stimuli, and unchanged for spontaneous spiking. This reflected the failure of standard detection during spatiotemporally dense spiking. Template-based detection revealed higher signal-to-noise ratio for sensory responses and sharper sensory tuning. Thus, this template matching method (and other model-based spike detection methods) critically improve the quantification of single-unit spiking activity.

neuroscience

Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models.

Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide the first systematic test of this hypothesis across 4 mouse models (Fmr1-/y, Cntnap2-/-, 16p11.2del/+, Tsc2+/-), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reductions in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization and spontaneous spiking were essentially normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo, despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype, but appears to reflect homeostatic stabilization of synaptic drive, rather than driving network hyperexcitability in autism.

neuroscience