Samuel Wilson Failor

Training in behavioral tasks can alter visual cortical stimulus coding, but the precise form of this plasticity is unclear. We measured orientation tuning in 4,000-neuron populations of mouse V1 before and after training on a visuomotor task. Changes to single-cell tuning curves were apparently complex, including appearance of asymmetric and multi-peaked tuning curves. Nevertheless, these changes reflected a simple mathematical transformation of population activity, suppressing responses to motor-associated stimuli specifically in cells responding at intermediate levels. The strength of the transformation varied across trials, suggesting a dynamic circuit mechanism rather than static synaptic plasticity. This transformation resulted in sparsening and orthogonalization of population codes for motor-associated stimuli. Training did not improve the performance of an optimal stimulus decoder, which was already perfect even for naïve codes, but the resulting orthogonalization improved the performance of a suboptimal decoder model with inductive bias as might be found in downstream readout circuits.

Background: Activity in neurons drives afferent competition that is critical for the refinement of nascent neural circuits. In ferrets, when an eye is lost in early development, surviving retinogeniculate afferents from the spared eye spread across the thalamus in a manner that is dependent on spontaneous retinal activity. However, how this spontaneous activity, also known as retinal waves, might dynamically regulate afferent terminal targeting remains unknown. Methods: We recorded retinal waves from retinae ex vivo using multi-electrode arrays. Retinae came from ferrets who were binocular or who had one eye surgically removed at birth. Linear mixed effects models were used to investigate the effects of early monocular enucleation on retinal wave activity. Results: When an eye is removed at birth, spontaneous bursts of action potentials by retinal ganglion cells (RGCs) in the surviving eye are shorter in duration. The shortening of RGC burst duration results in decreased pairwise RGC correlations across the retina and is associated with the retinal wave-dependent spread of retinogeniculate afferents previously reported in enucleates. Conclusion: Our findings show that removal of the competing eye modulates retinal waves and could underlie the dynamic regulation of competition-based refinement during retinogeniculate development.

Significance: Spontaneous neural activity is known to play a role in the maturation of nascent neural circuitry. Here we show for the first time a role for early spontaneous correlated retinal activity (i.e., retinal waves) in regulating the laminar targeting and functional development of the retinogeniculate pathway in the monocular condition—a condition where intereye competition and eye-specific segregation are not present. These findings demonstrate the importance of intraeye competition in early visual pathway circuit development. Our results provide a revision to the model of retinogeniculate development and to our general understanding of how neural activity guides the establishment of proper connectivity in the developing brain.

Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia–ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to −0.10 (p< 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 (p< 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field (p= 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation.