- Subcortical Source and Modulation of the Narrowband Gamma Oscillation in Mouse Visual Cortex. [Journal Article]
- NNeuron 2017 Jan 18; 93(2):315-322
- Primary visual cortex exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources...
Primary visual cortex exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources of the narrowband gamma oscillation, the factors modulating its strength, and its relationship to broadband gamma activity. Narrowband and broadband gamma power were uncorrelated. Increasing visual contrast had opposite effects on the two rhythms: it increased broadband activity, but suppressed the narrowband oscillation. The narrowband oscillation was strongest in layer 4 and was mediated primarily by excitatory currents entrained by the synchronous, rhythmic firing of neurons in the lateral geniculate nucleus (LGN). The power and peak frequency of the narrowband gamma oscillation increased with light intensity. Silencing the cortex optogenetically did not abolish the narrowband oscillation in either LGN firing or cortical excitatory currents, suggesting that this oscillation reflects unidirectional flow of signals from thalamus to cortex.
- Modulation of Fast Narrowband Oscillations in the Mouse Retina and dLGN According to Background Light Intensity. [Journal Article]
- NNeuron 2017 Jan 18; 93(2):299-307
- Background light intensity (irradiance) substantially impacts the visual code in the early visual system at synaptic and single-neuron levels, but its influence on population activity is largely unex...
Background light intensity (irradiance) substantially impacts the visual code in the early visual system at synaptic and single-neuron levels, but its influence on population activity is largely unexplored. We show that fast narrowband oscillations, an important feature of population activity, systematically increase in amplitude as a function of irradiance in both anesthetized and awake, freely moving mice and at the level of the retina and dorsal lateral geniculate nucleus (dLGN). Narrowband coherence increases with irradiance across large areas of the dLGN, but especially for neighboring units. The spectral sensitivity of these effects and their substantial reduction in melanopsin knockout animals indicate a contribution from inner retinal photoreceptors. At bright backgrounds, narrowband coherence allows pooling of single-unit responses to become a viable strategy for enhancing visual signals within its frequency range.
- Leukemia inhibitory factor impairs structural and neurochemical development of rat visual cortex in vivo. [Journal Article]
- MCMol Cell Neurosci 2017 Jan 11; 79:81-92
- Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocort...
Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo. Likewise, DIV 12-20 LIF treatment in organotypic cultures prevents somatic growth GABA-ergic neurons. Further, while NPY expression is increased in the LIF-infused hemispheres, the expression of parvalbumin mRNA and protein, Kv3.1 mRNA, calbindin D-28k protein, and GAD-65 mRNA, but not of GAD-67 mRNA or calretinin protein is substantially reduced. Also, LIF treatment decreases parvalbumin, Kv3.1, Kv3.2 and GAD-65, but not GAD-67 mRNA expression in OTC. Developing cortical neurons are known to depend on neurotrophins. Indeed, LIF alters neurotrophin mRNA expression, and prevents the growth promoting action of neurotophin-4 in GABA-ergic neurons. The results imply that LIF, by altering neurotrophin expression and/or signaling, could counteract neurotrophin-dependent growth and neurochemical differentiation of cortical neurons.
- Asymmetries of Dark and Bright Negative Afterimages Are Paralleled by Subcortical ON and OFF Post-Stimulus Responses. [Journal Article]
- JNJ Neurosci 2017 Jan 11
- Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiolog...
Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiological recordings in dorsal lateral-geniculate nucleus (dLGN) and primary visual cortex (V1) of cat and monkey. Specifically, V1 population responses demonstrate that darks elicit higher levels of activation than brights, and the latency of OFF responses in dLGN and V1 is shorter than that of ON responses. The removal of a dark or bright disc often generates the perception of a negative afterimage, and here we ask whether there also exist asymmetries for negative afterimages elicited by dark and bright discs. If so, do the post-stimulus responses of subcortical ON and OFF cells parallel such afterimage asymmetries? To test these hypotheses, we performed psychophysical experiments in humans and single-cell/s-potential recordings in cat dLGN. Psychophysically, we found that bright afterimages elicited by luminance decrements are stronger and last longer than dark afterimages elicited by luminance increments of equal sizes. Neurophysiologically, we found that ON cells responded to the removal of a dark disc with higher firing rates that were maintained for longer than OFF cells to the removal of a bright disc. The ON and OFF cell asymmetry was most pronounced at long stimulus durations in the dLGN. We conclude that subcortical response strength differences between ON and OFF channels parallel the asymmetries between bright and dark negative afterimages, further supporting a subcortical origin of bright and dark afterimage perception.
- Orientation selectivity in the visual cortex of the nine-banded armadillo. [Journal Article]
- JNJ Neurophysiol 2017 Jan 04; :jn.00851.2016
- Orientation selectivity in primary visual cortex (V1) has been proposed to reflect a canonical computation performed by the neocortical circuitry. While orientation selectivity has been reported in ...
Orientation selectivity in primary visual cortex (V1) has been proposed to reflect a canonical computation performed by the neocortical circuitry. While orientation selectivity has been reported in all mammals examined to date, the degree of selectivity and the functional organization of selectivity varies across clades. The differences in degree of orientation selectivity are large from reports in marsupials that only a small subset of neurons are selective to studies in carnivores in which it is rare to find a neuron lacking selectivity. Further, the functional organization in cortex varies in that the primate and carnivore V1 is characterized by an organization in which nearby neurons share orientation preference while other mammals such as rodents and lagomorphs either lack or have only extremely weak clustering. To gain insight into the evolutionary emergence of orientation selectivity we examined a member of Xenarthra, an early placental clade whose members are rod monochromats. Here, for the first time, we use a combination of neuroimaging, histological, and electrophysiological methods to identify the retinofugal pathways, locate V1, and examine the functional properties of V1 neurons in the armadillo (Dasypus novemcinctus) V1. Individual neurons were strongly sensitive to the orientation and often the direction of drifting gratings. We uncovered a wide range of orientation preferences, but found a bias for horizontal gratings. The presence of strong orientation selectivity in armadillo suggests that the circuitry responsible for this computation is common to placental mammals, and may reflect a difference in the cortical circuitry of marsupial and placental cohorts.
- Retinal and Nonretinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus. [Journal Article]
- JNJ Neurosci 2017 Jan 04; 37(1):226-235
- Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain ...
Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain control, and temporal features of visual responses. Despite evidence for the involvement of both retinal and nonretinal circuits in the generation of extraclassical suppression, we lack an understanding of the relative roles played by these pathways and how they interact during visual stimulation. To determine the contribution of retinal and nonretinal mechanisms to extraclassical suppression in the feline, we made simultaneous single-unit recordings from synaptically connected retinal ganglion cells and LGN neurons and measured the influence of stimulus size on the spiking activity of presynaptic and postsynaptic neurons. Results show that extraclassical suppression is significantly stronger for LGN neurons than for their retinal inputs, indicating a role for extraretinal mechanisms. Further analysis revealed that the enhanced suppression can be accounted for by mechanisms that suppress the effectiveness of retinal inputs in evoking LGN spikes. Finally, an examination of the time course for the onset of extraclassical suppression in the LGN and the size-dependent modulation of retinal spike efficacy suggests the early phase of augmented suppression involves local thalamic circuits. Together, these results demonstrate that the LGN is much more than a simple relay for retinal signals to cortex; it also filters retinal spikes dynamically on the basis of stimulus statistics to adjust the gain of visual signals delivered to cortex.
- Potential Role of Synaptic Activity to Inhibit LTD Induction in Rat Visual Cortex. [Journal Article]
- NPNeural Plast 2016; 2016:1401935
- Long-term depression (LTD), a widely studied form of activity-dependent synaptic plasticity, is typically induced by prolonged low-frequency stimulation (LFS). Interestingly, LFS is highly effective ...
Long-term depression (LTD), a widely studied form of activity-dependent synaptic plasticity, is typically induced by prolonged low-frequency stimulation (LFS). Interestingly, LFS is highly effective in eliciting LTD in vitro, but much less so under in vivo conditions; the reasons for the resistance of the intact brain to express LTD are not well understood. We examined if levels of background electrocorticographic (ECoG) activity influence LTD induction in the thalamocortical visual system of rats under very deep urethane anesthesia, inducing a brain state of reduced spontaneous cortical activity. Under these conditions, LFS applied to the lateral geniculate nucleus resulted in LTD of field postsynaptic potentials (fPSPs) recorded in the primary visual cortex (V1). Pairing LFS with stimulation of the brainstem (pedunculopontine) reticular formation resulted in the appearance of faster, more complex activity in V1 and prevented LTD induction, an effect that did not require muscarinic or nicotinic receptors. Reticular stimulation alone (without LFS) had no effect on cortical fPSPs. These results show that excitation of the brainstem activating system blocks the induction of LTD in V1. Thus, higher levels of neural activity may inhibit depression at cortical synapses, a hypothesis that could explain discrepancies regarding LTD induction in previous in vivo and in vitro work.
- Adaptive reorganization of retinogeniculate axon terminals in dorsal lateral geniculate nucleus following experimental mild traumatic brain injury. [Journal Article]
- ENExp Neurol 2016 Dec 28; 289:85-95
- The pathologic process in traumatic brain injury marked by delayed axonal loss, known as diffuse axonal injury (DAI), leads to partial deafferentation of neurons downstream of injured axons. This pro...
The pathologic process in traumatic brain injury marked by delayed axonal loss, known as diffuse axonal injury (DAI), leads to partial deafferentation of neurons downstream of injured axons. This process is linked to persistent visual dysfunction following mild traumatic brain injury (mTBI), however, examination of deafferentation in humans is impossible with current technology. To investigate potential reorganization in the visual system following mTBI, we utilized the central fluid percussion injury (cFPI) mouse model of mTBI. We report that in the optic nerve of adult male C57BL/6J mice, axonal projections of retinal ganglion cells (RGCs) to their downstream thalamic target, dorsal lateral geniculate nucleus (dLGN), undergo DAI followed by scattered, widespread axon terminals loss within the dLGN at 4days post-injury. However, at 10days post-injury, significant reorganization of RGC axon terminals was found, suggestive of an adaptive neuroplastic response. While these changes persisted at 20days post-injury, the RGC axon terminal distribution did not recovery fully to sham-injury levels. Our studies also revealed that following DAI, the segregation of axon terminals from ipsilateral and contralateral eye projections remained consistent with normal adult mouse distribution. Lastly, our examination of the shell and core of dLGN suggested that different RGC subpopulations may vary in their susceptibility to injury or in their contribution to reorganization following injury. Collectively, these findings support the premise that subcortical axon terminal reorganization may contribute to recovery following mTBI, and that different neural phenotypes may vary in their contribution to this reorganization despite exposure to the same injury.
- Novel Methodology for Creating Macaque Retinas with Sortable Photoreceptors and Ganglion Cells. [Journal Article]
- FNFront Neurosci 2016; 10:551
- Purpose: The ability to generate macaque retinas with sortable cell populations would be of great benefit to both basic and translational studies of the primate retina. The purpose of our study was t...
Purpose: The ability to generate macaque retinas with sortable cell populations would be of great benefit to both basic and translational studies of the primate retina. The purpose of our study was therefore to develop methods to achieve this goal by selectively labeling, in life, photoreceptors (PRs) and retinal ganglion cells (RGCs) with separate fluorescent markers. Methods: Labeling of macaque (Macaca fascicularis) PRs and RGCs was accomplished by subretinal delivery of AAV5-hGRK1-GFP, and retrograde transport of micro-ruby™ from the lateral geniculate nucleus, respectively. Retinas were anatomically separated into different regions. Dissociation conditions were optimized, and cells from each region underwent fluorescent activated cell sorting (FACS). Expression of retinal cell type- specific genes was assessed by quantitative real-time PCR to characterize isolated cell populations. Results: We show that macaque PRs and RGCs can be simultaneously labeled in-life and enriched populations isolated by FACS. Recovery from different retinal regions indicated efficient isolation/enrichment for PRs and RGCs, with the macula being particularly amendable to this technique. Conclusions: The methods and materials presented here allow for the identification of novel reagents designed to target RGCs and/or photoreceptors in a species that is phylogenetically and anatomically similar to human. These techniques will enable screening of intravitreally-delivered AAV capsid libraries for variants with increased tropism for PRs and/or RGCs and the evaluation of vector tropism and/or cellular promoter activity of gene therapy vectors in a clinically relevant species.
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- Focal Gain Control of Thalamic Visual Receptive Fields by Layer 6 Corticothalamic Feedback. [Journal Article]
- CCCereb Cortex 2016 Dec 17
- The projections between the thalamus and primary visual cortex (V1) are a key reciprocal neural circuit, relaying retinal signals to cortical layers 4 & 6 while being simultaneously regulated by mass...
The projections between the thalamus and primary visual cortex (V1) are a key reciprocal neural circuit, relaying retinal signals to cortical layers 4 & 6 while being simultaneously regulated by massive layer 6 corticothalamic feedback. Effectively dissecting the influence of this corticothalamic feedback circuit in higher mammals remains a challenge for vision research. By pharmacologically increasing the focal gain of visually driven layer 6 responses of cat V1 in a controlled fashion, we examined the effects of such focal cortical changes on the response amplitudes and spatial structure of the receptive fields (RFs) of individual dorsal lateral geniculate nucleus (dLGN) cells. We found that enhancing visually driven cortical feedback could facilitate or suppress the overall responses of dLGN cells, and such an effect was linked to the orientation preference of the cortical neuron. Related to these selective retinotopic gain changes, enhanced feedback induced the RFs of dLGN cells to expand, contract or shift their spatial focus. Our results provide further evidence for a functional mechanism through which the cortex can selectively gate visual information flow from the thalamus back to the visual cortex.