Disruption of layer 4 development alters laminar processing in ferret somatosensory cortex.

Treatment with the anti-mitotic agent methylazoxymethanol (MAM) on embryonic day 33 (E33) in ferrets changes features of somatosensory cortex. These include dramatic reduction of cells in layer 4, and altered distributions of thalamocortical afferent terminations and GABA(A) receptors. To determine the effect of the relative absence of layer 4 on processing of sensory stimuli we used current source-density profiles to assess laminar activity patterns. Nearly synchronous activation occurs across all layers in treated animals, which contrasts with the normal cortical activation pattern of initial sinks in layer 4. This change after MAM treatment is consistent with the absence of layer 4 cells and widespread termination of thalamocortical afferents. Using periodic stimulation at 'flutter' frequency, layer 4 neurons in normal somatosensory cortex fire reproducibly to the stimulus rate; the capacity for entrainment is best for layer 4 and weaker in the extragranular layers. The capacity to encode periodic sensory stimuli is disrupted in MAM-treated somatosensory cortex; after an initial response to the onset of periodic stimuli, neurons in all cortical layers show weak entrainment. Neural responses to sensory drive in E33 MAM-treated cortex are also embedded in levels of neural activity substantially above those in normal somatosensory cortex. Sustained stimulation additionally reveals different capacities in each layer for improved signal-to-noise ratios, with layer 4 neurons in normal animals exhibiting the most improved signaling over time. We conclude that normal thalamic terminations, an intact layer 4 and subsequent intracortical processing are integral to proper encoding of stimulus features.