Development of reciprocal connections between the dorsal lateral geniculate nucleus and the thalamic reticular nucleus.

The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development.Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2-4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2-4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4-6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry.

A non-image-forming visual circuit mediates the innate fear of heights in male mice.

The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

Spiking activity in the visual thalamus is coupled to pupil dynamics across temporal scales.

The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed a robust coupling between spiking activity in the mouse dorsolateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning a few seconds to several minutes. Throughout all these timescales, 2 distinct spiking modes-individual tonic spikes and tightly clustered bursts of spikes-preferred opposite phases of pupil dynamics. This multi-scale coupling reveals modulations distinct from those captured by pupil size per se, locomotion, and eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in the encoding of visual information. We conclude that dLGN spiking activity is under the simultaneous influence of multiple arousal-related processes associated with pupil dynamics occurring over a broad range of timescales.

Differential cortical and subcortical visual processing with eyes shut.

Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown. To understand how visual processing is modulated when eyes are shut, we used functional magnetic resonance imaging (fMRI) to measure responses to a flickering visual stimulus at high (100%) and low (10%) temporal contrasts, while participants viewed the stimuli with their eyes open or closed. Interestingly, we discovered that eye closure produced a qualitatively distinct pattern of effects across the visual thalamus and visual cortex. We found that with eyes open, low temporal contrast stimuli produced smaller responses across the lateral geniculate nucleus (LGN), primary (V1) and extrastriate visual cortex (V2). However, with eyes closed, we discovered that the LGN and V1 maintained similar blood oxygenation level-dependent (BOLD) responses as the eyes open condition, despite the suppressed visual input through the eyelid. In contrast, V2 and V3 had strongly attenuated BOLD response when eyes were closed, regardless of temporal contrast. Our findings reveal a qualitatively distinct pattern of visual processing when the eyes are closed-one that is not simply an overall attenuation but rather reflects distinct responses across visual thalamocortical networks, wherein the earliest stages of processing preserve information about stimuli but are then gated off downstream in visual cortex.NEW & NOTEWORTHY When we close our eyes coarse luminance information is still accessible by the visual system. Using functional magnetic resonance imaging, we examined whether eyelid closure plays a unique role in visual processing. We discovered that while the LGN and V1 show equivalent responses when the eyes are open or closed, extrastriate cortex exhibited attenuated responses with eye closure. This suggests that when the eyes are closed, downstream visual processing is blind to this information.

Transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus.

Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA sequencing and validated differentially expressed genes via quantitative polymerase chain reaction analysis. The rat model of tinnitus was established by analyzing startle behavior based on gap-pre-pulse inhibition of acoustic startles. We identified 87 differently expressed genes, of which 40 were upregulated and 47 were downregulated. Pathway-enrichment analysis revealed that the differentially enriched genes in the tinnitus group were associated with pathway terms, such as coronavirus disease COVID-19, neuroactive ligand-receptor interaction. Protein-protein-interaction networks were established, and two hub genes (Rpl7a and AC136661.1) were identified among the selected genes. Further studies focusing on targeting and modulating these genes are required for developing potential treatments for noise-induced tinnitus in patients.

Basic Properties of Coordinated Neuronal Ensembles in the Auditory Thalamus.

Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain.

Temporal Sensitivity for Achromatic and Chromatic Flicker across the Visual Cortex.

The retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic postreceptoral channels. The goal of the current study was to determine temporal sensitivity across the three postreceptoral channels in subcortical and cortical regions involved in human vision. We measured functional magnetic resonance imaging (fMRI) responses at 7 T from three participants (two males, one female) viewing a high-contrast, flickering, spatially uniform wide field (∼140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L + M + S, L - M, and S - (L + M) cone combinations. These measurements were used to create temporal sensitivity functions of the primary visual cortex (V1) across eccentricity and spatially averaged responses from the lateral geniculate nucleus (LGN), and the V2/V3, hV4, and V3A/B regions. fMRI responses reflected the known properties of the visual system, including higher peak temporal sensitivity to achromatic versus chromatic stimuli and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. The comparison of measured cortical responses to a model of the integrated retinal output to our stimuli demonstrates that extensive filtering and amplification are applied to postretinal signals.

Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.

Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.

Mouse auditory cortex sub-fields receive neuronal projections from MGB subdivisions independently.

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.

Adult Neurogenesis of the Medial Geniculate Body: In Vitro and Molecular Genetic Analyses Reflect the Neural Stem Cell Capacity of the Rat Auditory Thalamus over Time.

Neural stem cells (NSCs) have been recently identified in the neonatal rat medial geniculate body (MGB). NSCs are characterized by three cardinal features: mitotic self-renewal, formation of progenitors, and differentiation into all neuroectodermal cell lineages. NSCs and the molecular factors affecting them are particularly interesting, as they present a potential target for treating neurologically based hearing disorders. It is unclear whether an NSC niche exists in the rat MGB up to the adult stage and which neurogenic factors are essential during maturation. The rat MGB was examined on postnatal days 8, 12, and 16, and at the adult stadium. The cardinal features of NSCs were detected in MGB cells of all age groups examined by neurosphere, passage, and differentiation assays. In addition, real-time quantitative polymerase chain reaction arrays were used to compare the mRNA levels of 84 genes relevant to NSCs and neurogenesis. In summary, cells of the MGB display the cardinal features of NSCs up to the adult stage with a decreasing NSC potential over time. Neurogenic factors with high importance for MGB neurogenesis were identified on the mRNA level. These findings should contribute to a better understanding of MGB neurogenesis and its regenerative capacity.

Visual evoked potentials in multiple sclerosis: P100 latency and visual pathway damage including the lateral geniculate nucleus.

OBJECTIVE: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS). METHODS: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R2 (mR2). RESULTS: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR2 = 0.26), and less strongly with OR-WML (mR2 = 0.17), NAOR-FA (mR2 = 0.13) and pRNFL (mR2 = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR2 = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR2 = -0.56). CONCLUSIONS: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay. SIGNIFICANCE: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS.

Lateral geniculate body is spared of tau pathology in Pick disease.

The pathobiology of tau is of great importance for understanding the mechanisms of neurodegeneration in aging and age-associated disorders such as Alzheimer disease (AD) and frontotemporal dementias. It is critical to identify neuronal populations and brain regions that are vulnerable or resistant to tau pathological changes. Pick disease (PiD) is a three-repeat (3R) tauopathy that belongs to the group of frontotemporal lobar degenerations. The neuropathologic changes of PiD are characterized by globular tau-positive neuronal intracytoplasmic inclusions, called Pick bodies, in the granule cells of the dentate gyrus and frontal and temporal neocortices, and ballooned neurons, named Pick neurons, in the neocortex. In the present study, we examined 13 autopsy-confirmed cases of PiD. Using immunohistochemistry for phospho-tau (AT8) and 3R tau isoform, all PiD cases demonstrated extensive lesions involving the hippocampus and neocortex. However, the lateral geniculate body (LGB) is spared of significant tau lesions in contrast to the neighboring hippocampus and other thalamic nuclei. Only 1 PiD case (7.7%) had tau-positive neurons, and 4 cases had tau-positive neurites (31%) in the LGB. By contrast, the LGB does consistently harbor tau lesions in other tauopathies including progressive supranuclear palsy, corticobasal degeneration, and AD.

Parallel pathways carrying direction-and orientation-selective retinal signals to layer 4 of the mouse visual cortex.

Parallel visual pathways from the retina to the primary visual cortex (V1) via the lateral geniculate nucleus are common to many mammalian species, including mice, carnivores, and primates. However, it remains unclear which visual features present in both retina and V1 may be inherited from parallel pathways versus extracted by V1 circuits in the mouse. Here, using calcium imaging and rabies circuit tracing, we explore the relationships between tuning of layer 4 (L4) V1 neurons and their retinal ganglion cell (RGC) inputs. We find that subpopulations of L4 V1 neurons differ in their tuning for direction, orientation, spatial frequency, temporal frequency, and speed. Furthermore, we find that direction-tuned L4 V1 neurons receive input from direction-selective RGCs, whereas orientation-tuned L4 V1 neurons receive input from orientation-selective RGCs. These results suggest that direction and orientation tuning of V1 neurons may be partly inherited from parallel pathways originating in the retina.

The neural origin for asymmetric coding of surface color in the primate visual cortex.

The coding privilege of end-spectral hues (red and blue) in the early visual cortex has been reported in primates. However, the origin of such bias remains unclear. Here, we provide a complete picture of the end-spectral bias in visual system by measuring fMRI signals and spiking activities in macaques. The correlated end-spectral biases between the LGN and V1 suggest a subcortical source for asymmetric coding. Along the ventral pathway from V1 to V4, red bias against green peaked in V1 and then declined, whereas blue bias against yellow showed an increasing trend. The feedforward and recurrent modifications of end-spectral bias were further revealed by dynamic causal modeling analysis. Moreover, we found that the strongest end-spectral bias in V1 was in layer 4C[Formula: see text]. Our results suggest that end-spectral bias already exists in the LGN and is transmitted to V1 mainly through the parvocellular pathway, then embellished by cortical processing.

Transient expression of heavy-chain neurofilaments in the perigeniculate nucleus of cats.

The perigeniculate nucleus (PGN) is a visual part of the thalamic reticular nucleus modulating the information transfer between the lateral geniculate nucleus and the visual cortex. This study focused on the postnatal development of the PGN in cats, using the SMI-32 antibody, which recognizes non-phosphorylated heavy-chain neurofilaments responsible for neuronal structural maturation and is also used as a marker for motion processing, or Y, stream. We questioned whether transient neuronal populations exist in the PGN and can they possibly be related to the Y processing stream. We uncovered a transient, robust SMI-32 staining in the PGN of kittens aged 0-34 days with the significant decline in the cellular density of labeled cells in older animals. According to the double-labeling, in all examined age groups, perigeniculate SMI-32-immunopositive cells are part of the main parvalbumin-positive population. The maximal cellular density of the double-stained cells appeared in animals aged 10-28 days. We also revealed that the most significant growth of perigeniculate cells's soma occurred at three postnatal weeks. The possible link of our data to the development of the Y visual processing stream and to the heterogeneity of the perigeniculate neuronal population is also discussed.

Expression of early growth responsive gene-1 in the lateral geniculate body of kittens with amblyopia caused by monocular form deprivation.

OBJECTIVE: The expression of early growth responsive gene-1 (Egr-1) in the lateral geniculate body in the normal kittens and those affected with amblyopia caused by monocular visual deprivation was compared to explore the potential significance of Egr-1 in the pathogenesis of amblyopia. METHODS: A total of 30 healthy kittens were equally and randomly divided into the control (n = 15) and the deprivation group (n = 15). The kittens were raised in natural light and the right eyes of the deprived kittens were covered with a black opaque covering. Pattern visual evoked potential (PVEP) was measured before and 1, 3, and 5 weeks after covering. Five kittens from each group were randomly selected and euthanized with 2% sodium pentobarbital (100 mg/kg) during the 1st, 3rd and 5th week after covering. The expression of Egr-1 in the lateral geniculate body in the two groups was compared by performing immunohistochemistry and in situ hybridization. RESULTS: After three weeks of covering, PVEP detection indicated that the P100 wave latency in the deprivation group was significantly higher than that in the control group (P < 0.05), whereas the amplitude decreased markedly (P < 0.05). The number of the positive cells (P < 0.05) and mean optical density (P < 0.05) of Egr-1 protein expression in the lateral geniculate body of the deprivation group were found to be substantially lower in comparison to the normal group, as well as the number (P < 0.05) and mean optical density of Egr-1 mRNA-positive cells (P < 0.05). However, with increase of age, positive expression of Egr-1 in the control group showed an upward trend (P < 0.05), but this trend was not noted in the deprivation group (P > 0.05). CONCLUSIONS: Monocular form deprivation can lead to substantially decreased expressions of Egr-1 protein and mRNA in the lateral geniculate body, which in turn can affect the normal expression of neuronal functions in the lateral geniculate body, thereby promoting the occurrence and development of amblyopia.

The postnatal development of retinal projections in strepsirrhine galagos (Otolemur garnettii).

Here, we describe the postnatal development of retinal projections in galagos. Galagos are of special interest as they represent the understudied strepsirrhine branch (galagos, pottos, lorises, and lemurs) of the primate radiations. The projections of both eyes were revealed in each galago by injecting red or green cholera toxin subunit B (CTB) tracers into different eyes of galagos ranging from postnatal day 5 to adult. In the dorsal lateral geniculate nucleus, the magnocellular, parvocellular, and koniocellular layers were clearly labeled and identified by having inputs from the ipsilateral or contralateral eye at all ages. In the superficial layers of the superior colliculus, the terminations from the ipsilateral eye were just ventral to those from the contralateral eye at all ages. Other terminations at postnatal day 5 and later were in the pregeniculate nucleus, the accessory optic system, and the pretectum. As in other primates, a small retinal projection terminated in the posterior part of the pulvinar, which is known to project to the temporal visual cortex. This small projection from both eyes was most apparent on day 5 and absent in mature galagos. A similar reduction over postnatal maturation has been reported in marmosets, leading to the speculation that early retinal inputs to the pulvinar are responsible for the activation and early maturation of the middle temporal visual area, MT.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Microglia induce auditory dysfunction after status epilepticus in mice.

Auditory dysfunction and increased neuronal activity in the auditory pathways have been reported in patients with temporal lobe epilepsy, but the cellular mechanisms involved are unknown. Here, we report that microglia play a role in the disinhibition of auditory pathways after status epilepticus in mice. We found that neuronal activity in the auditory pathways, including the primary auditory cortex and the medial geniculate body (MGB), was increased and auditory discrimination was impaired after status epilepticus. We further demonstrated that microglia reduced inhibitory synapses on MGB relay neurons over an 8-week period after status epilepticus, resulting in auditory pathway hyperactivity. In addition, we found that local removal of microglia from the MGB attenuated the increase in c-Fos+ relay neurons and improved auditory discrimination. These findings reveal that thalamic microglia are involved in auditory dysfunction in epilepsy.

Enhancement and contextual modulation of visuospatial processing by thalamocollicular projections from ventral lateral geniculate nucleus.

In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic axons to the superior colliculus (SC). However, whether and how vLGN contributes to fundamental visual information processing remains largely unclear. Here, we report in mice that vLGN facilitates visually-guided approaching behavior mediated by the lateral SC and enhances the sensitivity of visual object detection. This can be attributed to the extremely broad spatial integration of vLGN neurons, as reflected in their much lower preferred spatial frequencies and broader spatial receptive fields than SC neurons. Through GABAergic thalamocollicular projections, vLGN specifically exerts prominent surround suppression of visuospatial processing in SC, leading to a fine tuning of SC preferences to higher spatial frequencies and smaller objects in a context-dependent manner. Thus, as an essential component of the central visual processing pathway, vLGN serves to refine and contextually modulate visuospatial processing in SC-mediated visuomotor behaviors via visually-driven long-range feedforward inhibition.