- Tectal-derived interneurons contribute to phasic and tonic inhibition in the visual thalamus. [Journal Article]
- NCNat Commun 2016 Dec 08; 7:13579
- The release of GABA from local interneurons in the dorsal lateral geniculate nucleus (dLGN-INs) provides inhibitory control during visual processing within the thalamus. It is commonly assumed that t...
The release of GABA from local interneurons in the dorsal lateral geniculate nucleus (dLGN-INs) provides inhibitory control during visual processing within the thalamus. It is commonly assumed that this important class of interneurons originates from within the thalamic complex, but we now show that during early postnatal development Sox14/Otx2-expressing precursor cells migrate from the dorsal midbrain to generate dLGN-INs. The unexpected extra-diencephalic origin of dLGN-INs sets them apart from GABAergic neurons of the reticular thalamic nucleus. Using optogenetics we show that at increased firing rates tectal-derived dLGN-INs generate a powerful form of tonic inhibition that regulates the gain of thalamic relay neurons through recruitment of extrasynaptic high-affinity GABAA receptors. Therefore, by revising the conventional view of thalamic interneuron ontogeny we demonstrate how a previously unappreciated mesencephalic population controls thalamic relay neuron excitability.
- Homonymous Sectoranopia: Asymptomatic Presentation of a Lateral Geniculate Nucleus Lesion. [Journal Article]
- NNeuroophthalmology 2015; 39(6):289-294
- This is a rare presentation of brain tumour in the region of the lateral geniculate nucleus (LGN) presenting as a homonymous horizontal sectoranopia (HHS). The case highlights that subtle field defec...
This is a rare presentation of brain tumour in the region of the lateral geniculate nucleus (LGN) presenting as a homonymous horizontal sectoranopia (HHS). The case highlights that subtle field defects can be asymptomatic and only detected by formal perimetry. Although homonymous sectoranopia is a rare form of visual field defect, it should be recognised as a potential manifestation of potentially significant intracranial pathology.
- Methylphenidate Enhances Early Stage Sensory Processing and Rodent Performance of a Visual Signal Detection Task. [Journal Article]
- NNeuropsychopharmacology 2016 Dec 02
- Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance enhancing agent in healthy individuals. MPH enhances catecholamine tra...
Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action impacts neural circuits performing cognitive and sensorimotor functions driving performance enhancement. The dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the cortex and is densely innervated by NE-containing fibers from the locus coeruleus (LC), a pathway known to modulate state-dependent sensory processing. Here, MPH was evaluated for its potential to alter stimulus-driven sensory responses and behavioral outcomes during performance of a visual signal detection task. MPH enhanced activity within individual neurons, ensembles of neurons, and visually-evoked potentials (VEPs) in response to task light cues, while increasing coherence within theta and beta oscillatory frequency bands. MPH also improved reaction times to make correct responses, indicating more efficient behavioral performance. Improvements in reaction speed were highly correlated with faster VEP latencies. Finally, immunostaining revealed that catecholamine innervation of the dLGN is solely noradrenergic. This work suggests that MPH, acting via noradrenergic mechanisms, can substantially impact early stage sensory signal processing and subsequent behavioral outcomes.Neuropsychopharmacology accepted article preview online, 02 December 2016. doi:10.1038/npp.2016.267.
- A Comparison of Visual Response Properties in the Lateral Geniculate Nucleus and Primary Visual Cortex of Awake and Anesthetized Mice. [Journal Article]
- JNJ Neurosci 2016 Nov 30; 36(48):12144-12156
- The cerebral cortex of the mouse has become one of the most important systems for studying information processing and the neural correlates of behavior. Multiple studies have examined the first stage...
The cerebral cortex of the mouse has become one of the most important systems for studying information processing and the neural correlates of behavior. Multiple studies have examined the first stages of visual cortical processing: primary visual cortex (V1) and its thalamic inputs from the dorsal lateral geniculate nucleus (dLGN), but more rarely in the lateral posterior nucleus (LP) in mice. Multiple single-unit surveys of dLGN and V1, both with electrophysiology and two-photon calcium imaging, have described receptive fields in anesthetized animals. Increasingly, awake animals are being used in physiological studies, so it is important to compare neuronal responses between awake and anesthetized state. We have performed a comprehensive survey of spatial and temporal response properties in V1, dLGN, and lateral posterior nucleus of both anesthetized and awake animals, using a common set of stimuli: drifting sine-wave gratings spanning a broad range of spatial and temporal parameters, and sparse noise stimuli consisting of flashed light and dark squares. Most qualitative receptive field parameters were found to be unchanged between the two states, such as most aspects of spatial processing, but there were significant differences in several parameters, most notably in temporal processing. Compared with anesthetized animals, the temporal frequency that evoked the peak response was shifted toward higher values in the dLGN of awake mice and responses were more sustained. Further, the peak response to a flashed stimulus was earlier in all three areas. Overall, however, receptive field properties in the anesthetized animal remain a good model for those in the awake animal.
- Retinal and Non-Retinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus. [Journal Article]
- JNJ Neurosci 2016 Nov 30
- 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 non-retinal 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 non-retinal 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 pre- and postsynaptic neurons. Results show that extraclassical suppression is significantly stronger for LGN neurons than for their retinal inputs, indicating a role for extra-retinal mechanisms. Further analysis reveals 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. Taken together, these results demonstrate that the LGN is much more than a simple relay for retinal signals to cortex; it dynamically filters retinal spikes on the basis of stimulus statistics to adjust the gain of visual signals delivered to cortex.
- Causal Role of Thalamic Interneurons in Brain State Transitions: A Study Using a Neural Mass Model Implementing Synaptic Kinetics. [Journal Article]
- FCFront Comput Neurosci 2016; 10:115
- Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons...
Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons, and constitute around 20-25% of the LGN cell population. However, there is a definite gap in knowledge about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay (TCR), thalamic reticular nucleus (TRN), to study the causality of IN on LGN oscillations and state-transitions. The synaptic information transmission in the model is implemented with kinetic modeling, facilitating the linking of low-level cellular attributes with high-level population dynamics. The model is parameterized and tuned to simulate alpha (8-13 Hz) rhythm that is dominant in both Local Field Potential (LFP) of LGN and electroencephalogram (EEG) of visual cortex in an awake resting state with eyes closed. The results show that: First, the response of the TRN is suppressed in the presence of IN in the circuit; disconnecting the IN from the circuit effects a dramatic change in the model output, displaying high amplitude synchronous oscillations within the alpha band in both TCR and TRN. These observations conform to experimental reports implicating the IN as the primary inhibitory modulator of LGN dynamics in a cognitive state, and that reduced cognition is achieved by suppressing the TRN response. Second, the model validates steady state visually evoked potential response in humans corresponding to periodic input stimuli; however, when the IN is disconnected from the circuit, the output power spectra do not reflect the input frequency. This agrees with experimental reports underpinning the role of IN in efficient retino-geniculate information transmission. Third, a smooth transition from alpha to theta band is observed by progressive decrease of neurotransmitter concentrations in the synaptic clefts; however, the transition is abrupt with removal of the IN circuitry in the model. The results imply a role of IN toward maintaining homeostasis in the LGN by suppressing any instability that may arise due to anomalous synaptic attributes.
- Cell type-specific expression of FoxP2 in the ferret and mouse retina. [Journal Article]
- NRNeurosci Res 2016 Nov 22
- Although the anatomical and physiological properties of subtypes of retinal ganglion cells (RGCs) have been extensively investigated, their molecular properties are still unclear. Here, we examined t...
Although the anatomical and physiological properties of subtypes of retinal ganglion cells (RGCs) have been extensively investigated, their molecular properties are still unclear. Here, we examined the expression patterns of FoxP2 in the retina of ferrets and mice. We found that FoxP2 was expressed in small subsets of neurons in the adult ferret retina. FoxP2-positive neurons in the ganglion cell layer were divided into two groups. Large FoxP2-positive neurons expressed Brn3a and were retrogradely labeled with cholera toxin subunit B injected into the optic nerve, indicating that they are RGCs. The soma size and the projection pattern of FoxP2-positive RGCs were consistent with those of X cells. Because we previously reported that FoxP2 was selectively expressed in X cells in the ferret lateral geniculate nucleus (LGN), our findings indicate that FoxP2 is specifically expressed in the parvocellular pathway from the retina to the LGN. Small FoxP2-positive neurons were positive for GAD65/67, suggesting that they are GABAergic amacrine cells. Most Foxp2-positive cells were RGCs in the adult mouse retina. Dendritic morphological analyses suggested that Foxp2-positive RGCs included direction-selective RGCs in mice. Thus, our findings suggest that FoxP2 is expressed in specific subtypes of RGCs in the retina of ferrets and mice.
- Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas. [Journal Article]
- PNProc Natl Acad Sci U S A 2016 Dec 06; 113(49):14139-14144
- A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual c...
A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of visual acuity is also fully reversed by binocular experience following treatment and, further, that prolonged retinal inactivation alone can erase anatomical consequences of MD. We conclude that temporary retinal inactivation represents a highly efficacious means to promote recovery of function.
- Functional symmetry of the primary visual pathway evidenced by steady-state visual evoked potentials. [Journal Article]
- BRBrain Res Bull 2016 Nov 12; 128:13-21
- The primary visual pathway exhibits a symmetrical anatomical structure, initially arising from the left and right retinas, passing through the lateral geniculate nucleus, and finally projecting to th...
The primary visual pathway exhibits a symmetrical anatomical structure, initially arising from the left and right retinas, passing through the lateral geniculate nucleus, and finally projecting to the left and right primary visual cortices. However, to our knowledge, studies based on scalp EEG have not provided adequate evidence of the functional symmetry of the primary visual pathway, as the usual visual ERP is often related to other higher-level brain areas. Steady-state visual evoked potentials (SSVEPs) can be considered as the direct response of the primary visual pathway to a repetitive stimulus, with a very limited correlation with responses of higher-level brain areas. Therefore, SSVEPs can be used to evaluate the functional symmetry of the primary visual pathway. In this study, we draw a comparison among the powers and distributions of SSVEPs of different frequencies when the left or right eye alone is stimulated, and when both the eyes are stimulated together. Our results indicate that the primary visual pathway is almost symmetrical in generating SSVEPs from either eye and that there is some functional interaction between the left and right primary visual pathways.
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- Perceptual Learning of Contrast Detection in the Human Lateral Geniculate Nucleus. [Journal Article]
- CBCurr Biol 2016 Dec 05; 26(23):3176-3182
- The brain is continuously modified by perceptual experience throughout life. Perceptual learning, which refers to the long-term performance improvement resulting from practice, has been widely used a...
The brain is continuously modified by perceptual experience throughout life. Perceptual learning, which refers to the long-term performance improvement resulting from practice, has been widely used as a paradigm to study experience-dependent brain plasticity in adults [1, 2]. In the visual system, adult plasticity is largely believed to be restricted to the cortex, with subcortical structures losing their capacity for change after a critical period of development [3, 4]. Although various cortical mechanisms have been shown to mediate visual perceptual learning [5-12], there has been no reported investigation of perceptual learning in subcortical nuclei. Here, human subjects were trained on a contrast detection task for 30 days, leading to a significant contrast sensitivity improvement that was specific to the trained eye and the trained visual hemifield. Training also resulted in an eye- and hemifield-specific fMRI signal increase to low-contrast patterns in the magnocellular layers of the lateral geniculate nucleus (LGN), even when subjects did not pay attention to the patterns. Such an increase was absent in the parvocellular layers of the LGN and visual cortical areas. Furthermore, the behavioral benefit significantly correlated with the neural enhancement. These findings suggest that LGN signals can be amplified by training to detect faint patterns. Neural plasticity induced by perceptual learning in human adults might not be confined to the cortical level but might occur as early as at the thalamic level.