Contrast and Luminance Gain Control in the Macaque's Lateral Geniculate Nucleus.

There is substantial variation in the mean and variance of light levels (luminance and contrast) in natural visual scenes. Retinal ganglion cells maintain their sensitivity despite this variation using two adaptive mechanisms, which control how responses depend on luminance and on contrast. However, the nature of each mechanism and their interactions downstream of the retina are unknown. We recorded neurons in the magnocellular and parvocellular layers of the lateral geniculate nucleus (LGN) in anesthetized adult male macaques and characterized how their responses adapt to changes in contrast and luminance. As contrast increases, neurons in the magnocellular layers maintain sensitivity to high temporal frequency stimuli but attenuate sensitivity to low-temporal frequency stimuli. Neurons in the parvocellular layers do not adapt to changes in contrast. As luminance increases, both magnocellular and parvocellular cells increase their sensitivity to high-temporal frequency stimuli. Adaptation to luminance is independent of adaptation to contrast, as previously reported for LGN neurons in the cat. Our results are similar to those previously reported for macaque retinal ganglion cells, suggesting that adaptation to luminance and contrast result from two independent mechanisms that are retinal in origin.

Morphological evidence for multiple distinct channels of corticogeniculate feedback originating in mid-level extrastriate visual areas of the ferret.

Complementary reciprocal feedforward and feedback circuits connecting the visual thalamus with the visual cortex are essential for visual perception. These circuits predominantly connect primary and secondary visual cortex with the dorsal lateral geniculate nucleus (LGN). Although there are direct geniculocortical inputs to extrastriate visual cortex, whether reciprocal corticogeniculate neurons exist in extrastriate cortex is not known. Here we utilized virus-mediated retrograde tracing to reveal the presence of corticogeniculate neurons in three mid-level extrastriate visual cortical areas in ferrets: PMLS, PLLS, and 21a. We observed corticogeniculate neurons in all three extrastriate areas, although the density of virus-labeled corticogeniculate neurons in extrastriate cortex was an order of magnitude less than that in areas 17 and 18. A cluster analysis of morphological metrics quantified following reconstructions of the full dendritic arborizations of virus-labeled corticogeniculate neurons revealed six distinct cell types. Similar corticogeniculate cell types to those observed in areas 17 and 18 were also observed in PMLS, PLLS, and 21a. However, these unique cell types were not equally distributed across the three extrastriate areas. The majority of corticogeniculate neurons per cluster originated in a single area, suggesting unique parallel organizations for corticogeniculate feedback from each extrastriate area to the LGN. Together, our findings demonstrate direct feedback connections from mid-level extrastriate visual cortex to the LGN, supporting complementary reciprocal circuits at multiple processing stages along the visual hierarchy. Importantly, direct reciprocal connections between the LGN and extrastriate cortex, that bypass V1, could provide a substrate for residual vision following V1 damage.

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.

Corticogeniculate feedback sharpens the temporal precision and spatial resolution of visual signals in the ferret.

The corticogeniculate (CG) pathway connects the visual cortex with the visual thalamus (LGN) in the feedback direction and enables the cortex to directly influence its own input. Despite numerous investigations, the role of this feedback circuit in visual perception remained elusive. To probe the function of CG feedback in a causal manner, we selectively and reversibly manipulated the activity of CG neurons in anesthetized ferrets in vivo using a combined viral-infection and optogenetics approach to drive expression of channelrhodopsin2 (ChR2) in CG neurons. We observed significant increases in temporal precision and spatial resolution of LGN neuronal responses to drifting grating and white noise stimuli when CG neurons expressing ChR2 were light activated. Enhancing CG feedback reduced visually evoked response latencies, increased spike-timing precision, and reduced classical receptive field size. Increased precision among LGN neurons led to increased spike-timing precision among granular layer V1 neurons as well. Together, our findings suggest that the function of CG feedback is to control the timing and precision of thalamic responses to incoming visual signals.

A cross-species comparison of corticogeniculate structure and function.

The corticogeniculate circuit is an evolutionarily conserved pathway linking the primary visual cortex with the visual thalamus in the feedback direction. While the corticogeniculate circuit is anatomically robust, the impact of corticogeniculate feedback on the visual response properties of visual thalamic neurons is subtle. Accordingly, discovering the function of corticogeniculate feedback in vision has been a particularly challenging task. In this review, the morphology, organization, physiology, and function of corticogeniculate feedback is compared across mammals commonly studied in visual neuroscience: primates, carnivores, rabbits, and rodents. Common structural and organizational motifs are present across species, including the organization of corticogeniculate feedback into parallel processing streams in highly visual mammals.

A sodium-pump-mediated afterhyperpolarization in pyramidal neurons.

The sodium-potassium ATPase (i.e., the "sodium pump") plays a central role in maintaining ionic homeostasis in all cells. Although the sodium pump is intrinsically electrogenic and responsive to dynamic changes in intracellular sodium concentration, its role in regulating neuronal excitability remains unclear. Here we describe a physiological role for the sodium pump in regulating the excitability of mouse neocortical layer 5 and hippocampal CA1 pyramidal neurons. Trains of action potentials produced long-lasting (∼20 s) afterhyperpolarizations (AHPs) that were insensitive to blockade of voltage-gated calcium channels or chelation of intracellular calcium, but were blocked by tetrodotoxin, ouabain, or the removal of extracellular potassium. Correspondingly, the AHP time course was similar to the decay of activity-induced increases in intracellular sodium, whereas intracellular calcium decayed at much faster rates. To determine whether physiological patterns of activity engage the sodium pump, we replayed in vitro a place-specific burst of 15 action potentials recorded originally in vivo in a CA1 "place cell" as the animal traversed the associated place field. In both layer 5 and CA1 pyramidal neurons, this "place cell train" generated small, long-lasting AHPs capable of reducing neuronal excitability for many seconds. Place-cell-train-induced AHPs were blocked by ouabain or removal of extracellular potassium, but not by intracellular calcium chelation. Finally, we found calcium contributions to the AHP to be temperature dependent: prominent at room temperature, but largely absent at 35°C. Our results demonstrate a previously unappreciated role for the sodium-potassium ATPase in regulating the excitability of neocortical and hippocampal pyramidal neurons.