Optic Tract Shrinkage Limits Visual Restoration After Occipital Stroke.

Background and Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral visual hemifield, initiating a process of trans-synaptic retrograde degeneration. The present study examined functional implications of this process, asking if degeneration impacted the amount of visual recovery attainable from visual restoration training in chronic patients, and if restoration training impacted optic tract (OT) shrinkage. Methods: Magnetic resonance imaging was used to measure OT volumes bilaterally in 36 patients with unilateral occipital stroke. From OT volumes, we computed laterality indices (LI), estimating the stroke-induced OT shrinkage in each case. A subset of these chronic patients (n=14, 13±6 months poststroke) underwent an average of nearly 1 year of daily visual restoration training, which repeatedly stimulated vision in their blind field. The amount of visual field recovery was quantified using Humphrey perimetry, and post training magnetic resonance imaging was used to assess the impact of training on OT shrinkage. Results: OT LI was correlated with time since stroke: it was close to 0 (no measurable OT shrinkage) in subacute participants (<6 months poststroke) while chronic participants (>6 months poststroke) exhibited LI >0, but with significant variability. Visual training did not systematically alter LI, but chronic patients with baseline LI≈0 (no OT shrinkage) exhibited greater visual field recovery than those with LI>0. Conclusions: Unilateral OT shrinkage becomes detectable with magnetic resonance imaging by ≈7 months poststroke, albeit with significant interindividual variability. Although visual restoration training did not alter the amount of degeneration already sustained, OT shrinkage appeared to serve as a biomarker of the potential for training-induced visual recovery in chronic cortically blind patients.

Loss of P2Y12 Has Behavioral Effects in the Adult Mouse.

While microglia have been established as critical mediators of synaptic plasticity, the molecular signals underlying this process are still being uncovered. Increasing evidence suggests that microglia utilize these signals in a temporally and regionally heterogeneous manner. Subsequently, it is necessary to understand the conditions under which different molecular signals are employed by microglia to mediate the physiological process of synaptic remodeling in development and adulthood. While the microglial purinergic receptor P2Y12 is required for ocular dominance plasticity, an adolescent form of experience-dependent plasticity, it remains unknown whether P2Y12 functions in other forms of plasticity at different developmental time points or in different brain regions. Using a combination of ex vivo characterization and behavioral testing, we examined how the loss of P2Y12 affects developmental processes and behavioral performance in adulthood in mice. We found P2Y12 was not required for an early form of plasticity in the developing visual thalamus and did not affect microglial migration into barrels in the developing somatosensory cortex. In adult mice, however, the loss of P2Y12 resulted in alterations in recognition and social memory, as well as anxiety-like behaviors, suggesting that while P2Y12 is not a universal regulator of synaptic plasticity, the loss of P2Y12 is sufficient to cause functional defects.

Optogenetic activation of corticogeniculate feedback stabilizes response gain and increases information coding in LGN neurons.

In spite of their anatomical robustness, it has been difficult to establish the functional role of corticogeniculate circuits connecting primary visual cortex with the lateral geniculate nucleus of the thalamus (LGN) in the feedback direction. Growing evidence suggests that corticogeniculate feedback does not directly shape the spatial receptive field properties of LGN neurons, but rather regulates the timing and precision of LGN responses and the information coding capacity of LGN neurons. We propose that corticogeniculate feedback specifically stabilizes the response gain of LGN neurons, thereby increasing their information coding capacity. Inspired by early work by McClurkin et al. (1994), we manipulated the activity of corticogeniculate neurons to test this hypothesis. We used optogenetic methods to selectively and reversibly enhance the activity of corticogeniculate neurons in anesthetized ferrets while recording responses of LGN neurons to drifting gratings and white noise stimuli. We found that optogenetic activation of corticogeniculate feedback systematically reduced LGN gain variability and increased information coding capacity among LGN neurons. Optogenetic activation of corticogeniculate neurons generated similar increases in information encoded in LGN responses to drifting gratings and white noise stimuli. Together, these findings suggest that the influence of corticogeniculate feedback on LGN response precision and information coding capacity could be mediated through reductions in gain variability.

Physiological characterization of a rare subpopulation of doublet-spiking neurons in the ferret lateral geniculate nucleus.

Interest in exploring homologies in the early visual pathways of rodents, carnivores, and primates has recently grown. Retinas of these species contain morphologically and physiologically heterogeneous retinal ganglion cells that form the basis for parallel visual information processing streams. Whether rare retinal ganglion cells with unusual visual response properties in carnivores and primates project to the visual thalamus and drive unusual visual responses among thalamic relay neurons is poorly understood. We surveyed neurophysiological responses among hundreds of lateral geniculate nucleus (LGN) neurons in ferrets and observed a novel subpopulation of LGN neurons displaying doublet-spiking waveforms. Some visual response properties of doublet-spiking LGN neurons, like contrast and temporal frequency tuning, were intermediate to those of X and Y LGN neurons. Interestingly, most doublet-spiking LGN neurons were tuned for orientation and displayed direction selectivity for horizontal motion. Spatiotemporal receptive fields of doublet-spiking neurons were diverse and included center/surround organization, On/Off responses, and elongated separate On and Off subregions. Optogenetic activation of corticogeniculate feedback did not alter the tuning or spatiotemporal receptive fields of doublet-spiking neurons, suggesting that their unusual tuning properties were inherited from retinal inputs. The doublet-spiking LGN neurons were found throughout the depth of LGN recording penetrations. Together these findings suggest that while extremely rare (<2% of recorded LGN neurons), unique subpopulations of LGN neurons in carnivores receive retinal inputs that confer them with nonstandard visual response properties like direction selectivity. These results suggest that neuronal circuits for nonstandard visual computations are common across a variety of species, even though their proportions vary.NEW & NOTEWORTHY Interest in visual system homologies across species has recently increased. Across species, retinas contain diverse retinal ganglion cells including cells with unusual visual response properties. It is unclear whether rare retinal ganglion cells in carnivores project to and drive similarly unique visual responses in the visual thalamus. We discovered a rare subpopulation of thalamic neurons defined by unique spike shape and visual response properties, suggesting that nonstandard visual computations are common to many species.

Morphological heterogeneity among corticogeniculate neurons in ferrets: quantification and comparison with a previous report in macaque monkeys.

The corticogeniculate (CG) pathway links the visual cortex with the lateral geniculate nucleus (LGN) of the thalamus and is the first feedback connection in the mammalian visual system. Whether functional connections between CG neurons and LGN relay neurons obey or ignore the separation of feedforward visual signals into parallel processing streams is not known. Accordingly, there is some debate about whether CG neurons are morphologically heterogeneous or homogenous. Here we characterized the morphology of CG neurons in the ferret, a visual carnivore with distinct feedforward parallel processing streams, and compared the morphology of ferret CG neurons with CG neuronal morphology previously described in macaque monkeys [Briggs et al. (2016) Neuron, 90, 388]. We used a G-deleted rabies virus as a retrograde tracer to label CG neurons in adult ferrets. We then reconstructed complete dendritic morphologies for a large sample of virus-labeled CG neurons. Quantification of CG morphology revealed three distinct CG neuronal subtypes with striking similarities to the CG neuronal subtypes observed in macaques. These findings suggest that CG neurons may be morphologically diverse in a variety of highly visual mammals in which feedforward visual pathways are organized into parallel processing streams. Accordingly, these results provide support for the notion that CG feedback is functionally parallel stream-specific in ferrets and macaques.

The function of Drosophila larval class IV dendritic arborization sensory neurons in the larval-pupal transition is separable from their function in mechanical nociception responses.

The sensory and physiological inputs which govern the larval-pupal transition in Drosophila, and the neuronal circuity that integrates them, are complex. Previous work from our laboratory identified a dosage-sensitive genetic interaction between the genes encoding the Rho-GEF Trio and the zinc-finger transcription factor Sequoia that interfered with the larval-pupal transition. Specifically, we reported heterozygous mutations in sequoia (seq) dominantly exacerbated the trio mutant phenotype, and this seq-enhanced trio mutant genotype blocked the transition of third instar larvae from foragers to wanderers, a requisite behavioral transition prior to pupation. In this work, we use the GAL4-UAS system to rescue this phenotype by tissue-specific trio expression. We find that expressing trio in the class IV dendritic arborization (da) sensory neurons rescues the larval-pupal transition, demonstrating the reliance of the larval-pupal transition on the integrity of these sensory neurons. As nociceptive responses also rely on the functionality of the class IV da neurons, we test mechanical nociceptive responses in our mutant and rescued larvae and find that mechanical nociception is separable from the ability to undergo the larval-pupal transition. This demonstrates for the first time that the roles of the class IV da neurons in governing two critical larval behaviors, the larval-pupal transition and mechanical nociception, are functionally separable from each other.

Visual speed sensitivity in the drum corps color guard.

Drum corps color guard experts spend years developing skills in spinning rifles, sabers, and flags. Their expertise provides a unique window into factors that govern sensitivity to the speed of rotational and radial motion. Prior neurophysiological research demonstrates that rotational and radial motion register in the Medial Superior Temporal (MST) region of the primate visual system. To the extent that shared neural events govern rotational and radial speed sensitivity, one would expect expertise on either task to transfer to the other. One similarly would expect shared neural events to generate correlations between rotational and radial speed sensitivity. We evaluated these predictions via visual speed sensitivity tests on drum corps color guard experts, drum corps low brass experts, and other age-matched control participants. Displays comprised bilaterally presented plaid patterns that rotated, radiated, or both. Participants reported which side contained faster motion. The data revealed a modest but reliably reproducible and specific group-by-task interaction; color guard speed sensitivity exhibited a rotational motion advantage and radial motion disadvantage. Additionally, rotational and radial speed sensitivity failed to predict each other significantly. Overall, the findings match predictions that follow from a dissociation between the neural events governing rotational and radial speed sensitivity.