Publications using TDT

Retinal prostheses have been developed to restore a functional form of vision in patients affected by outer retinal layer dystrophies. Other approaches, namely optic nerve, thalamic, and cortical prostheses are under investigation to expand this toolbox both as clinical devices and as tools for fundamental research. Optic nerve stimulation is attractive since it bypasses the entire retinal network and directly activates nerve fibers. At the same time, it still takes advantage of the high-level information processing occurring downstream in the visual cortex. Here we show that a new intraneural electrode array (OpticSELINE) is effective in inducing the activation of the visual cortex upon electrical stimulation of the optic nerve. We also demonstrate that intraneural optic nerve stimulation induces selective cortical activation patterns depending on the stimulating electrode, thus suggesting that the OpticSELINE possesses spatial selectivity in fiber stimulation. In conclusion, the OpticSELINE can be used both as visual prosthesis for blind patients and as tool to further investigate the effect of the electrical stimulation in the visual system.

Ultrasound that is widely used in medical diagnosis has drawn growing interests as a noninvasive means of neuromodulation. Focused pulsed ultrasound (FPUS) effectively modulates neural encoding and transmission in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes from recordings of compound action potentials (CAP). To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the neuromodulation effects of FPUS on individual axon. Unlike previous CAP recordings, our single-unit recordings afford superior spatial and temporal resolution to reveal the subtle but consistent effects of ultrasonic neuromodulation. Our results indicate that, (1) FPUS did not evoke action potentials directly in mouse sciatic nerve at all the tested intensities (spatial peak temporal average intensity, I SPTA of 0.91 to 28.2 W/cm 2 ); (2) FPUS increases the nerve conduction velocity (CV) in both fast-conducting A- and slow-conducting C- type axons with effects more pronounced at increased stimulus duration and intensity; and (3) effects of increased CV is reversible and cannot be attributed to the change of local temperature. Our results support existing theories of non-thermal mechanisms underlying ultrasonic neuromodulation with low-intensity FPUS, including NICE, flexoelectricity, and solition models. This work also provides a solid experimental basis to further advance our mechanistic understandings of ultrasonic neuromodulation in the PNS.

We present a new class of carbon-based neural probes that consist of homogeneous glassy carbon (GC) microelectrodes, interconnects and bump pads. These electrodes have purely capacitive behavior with exceptionally high charge storage capacity (CSC) and are capable of sustaining more than 3.5 billion cycles of bi-phasic pulses at charge density of 0.25 mC/cm 2 . These probes enable both high SNR (>16) electrical signal recording and remarkably high-resolution real-time neurotransmitter detection, on the same platform. Leveraging a new 2-step, double-sided pattern transfer method for GC structures, these probes allow extended long-term electrical stimulation with no electrode material corrosion. Cross-section characterization through FIB and SEM imaging demonstrate strong attachment enabled by hydroxyl and carbonyl covalent bonds between GC microstructures and top insulating and bottom substrate layers. Extensive in-vivo and in-vitro tests confirmed: (i) high SNR (>16) recordings, (ii) highest reported CSC for non-coated neural probe (61.4 ± 6.9 mC/cm 2 ), (iii) high-resolution dopamine detection (10 nM level - one of the lowest reported so far), (iv) recording of both electrical and electrochemical signals, and (v) no failure after 3.5 billion cycles of pulses. Therefore, these probes offer a compelling multi-modal platform for long-term applications of neural probe technology in both experimental and clinical neuroscience.

The integration of excitatory and inhibitory synaptic inputs is fundamental to neuronal processing. In the mammalian auditory brainstem, neurons compare excitatory and inhibitory inputs from the ipsilateral and contralateral ear, respectively, for sound localization. However, the temporal precision and functional roles of inhibition in this integration process are unclear. Here, we demonstrate by in vivo recordings from the lateral superior olive (LSO) that inhibition controls spiking with microsecond precision throughout high frequency click trains. Depending on the relative timing of excitation and inhibition, neuronal spike probability is either suppressed or—unexpectedly—facilitated. In vitro conductance-clamp LSO recordings establish that a reduction in the voltage threshold for spike initiation due to a prior hyperpolarization results in post-inhibitory facilitation of otherwise sub-threshold synaptic events. Thus, microsecond-precise differences in the arrival of inhibition relative to excitation can facilitate spiking in the LSO, thereby promoting spatial sensitivity during the processing of faint sounds.

Observational learning is a powerful survival tool allowing individuals to learn about threat-predictive stimuli without directly experiencing the pairing of the predictive cue and punishment. This ability has been linked to the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA). To investigate how information is encoded and transmitted through this circuit, we performed electrophysiological recordings in mice observing a demonstrator mouse undergo associative fear conditioning and found that BLA-projecting ACC (ACC→BLA) neurons preferentially encode socially derived aversive cue information. Inhibition of ACC→BLA alters real-time amygdala representation of the aversive cue during observational conditioning. Selective inhibition of the ACC→BLA projection impaired acquisition, but not expression, of observational fear conditioning. We show that information derived from observation about the aversive value of the cue is transmitted from the ACC to the BLA and that this routing of information is critically instructive for observational fear conditioning. VIDEO ABSTRACT.

Objectives: This study was designed to evaluate binaural temporal processing in young and older adults using a binaural masking level difference (BMLD) paradigm. Using behavioral and electrophysiological measures within the same listeners, a series of stimulus manipulations was used to evaluate the relative contribution of binaural temporal fine-structure and temporal envelope cues. We evaluated the hypotheses that age-related declines in the BMLD task would be more strongly associated with temporal fine-structure than envelope cues and that age-related declines in behavioral measures would be correlated with cortical auditory evoked potential (CAEP) measures. Design: Thirty adults participated in the study, including 10 young normal-hearing, 10 older normal-hearing, and 10 older hearing-impaired adults with bilaterally symmetric, mild-to-moderate sensorineural hearing loss. Behavioral and CAEP thresholds were measured for diotic (So) and dichotic (Sπ) tonal signals presented in continuous diotic (No) narrowband noise (50-Hz wide) maskers. Temporal envelope cues were manipulated by using two different narrowband maskers; Gaussian noise (GN) with robust envelope fluctuations and low-noise noise (LNN) with minimal envelope fluctuations. The potential to use temporal fine-structure cues was controlled by varying the signal frequency (500 or 4000 Hz), thereby relying on the natural decline in phase-locking with increasing frequency. Results: Behavioral and CAEP thresholds were similar across groups for diotic conditions, while the masking release in dichotic conditions was larger for younger than for older participants. Across all participants, BMLDs were larger for GN than LNN and for 500-Hz than for 4000-Hz conditions, where envelope and fine-structure cues were most salient, respectively. Specific age-related differences were demonstrated for 500-Hz dichotic conditions in GN and LNN, reflecting reduced binaural temporal fine-structure coding. No significant age effects were observed for 4000-Hz dichotic conditions, consistent with similar use of binaural temporal envelope cues across age in these conditions. For all groups, thresholds and derived BMLD values obtained using the behavioral and CAEP methods were strongly correlated, supporting the notion that CAEP measures may be useful as an objective index of age-related changes in binaural temporal processing. Conclusions: These results demonstrate an age-related decline in the processing of binaural temporal fine-structure cues with preserved temporal envelope coding that was similar with and without mild-to-moderate peripheral hearing loss. Such age-related changes can be reliably indexed by both behavioral and CAEP measures in young and older adults.

Forward masking experiments at 4 kHz have demonstrated that preceding sound can elicit changes in masking patterns consistent with a change in cochlear gain. However, the acoustic environment is filled with complex sounds, often dominated by lower frequencies, and ipsilateral cochlear gain reduction at frequencies below 4 kHz is largely unstudied in the forward masking literature. In this experiment, the magnitude of ipsilateral cochlear gain reduction was explored at 1, 2, and 4 kHz using forward masking techniques in an effort to evaluate a range of frequencies in listeners with normal hearing. Gain reduction estimates were not significantly different at 2 and 4 kHz using two forward masking measurements. Although the frequency was a significant factor in the analysis, post hoc testing supported the interpretation that gain reduction estimates measured without a masker were not significantly different at 1, 2, and 4 kHz. A second experiment provided evidence that forward masking in this paradigm at 1 kHz cannot be explained by excitation alone. This study provides evidence of ipsilateral cochlear gain reduction in humans at frequencies below the 4 kHz region.

Objectives: The medial olivocochlear (MOC) efferent system can modify cochlear function to improve sound detection in noise, but its role in speech perception in noise is unclear. The purpose of this study was to determine the association between MOC efferent activity and performance on two speech-in-noise tasks at two signal-to-noise ratios (SNRs). It was hypothesized that efferent activity would be more strongly correlated with performance at the more challenging SNR, relative to performance at the less challenging SNR. Design: Sixteen adults aged 35 to 73 years participated. Subjects had pure-tone averages ≤25 dB HL and normal middle ear function. High-frequency pure-tone averages were computed across 3000 to 8000 Hz and ranged from 6.3 to 48.8 dB HL. Efferent activity was assessed using contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) measured in right ears, and MOC activation was achieved by presenting broadband noise to left ears. Contralateral suppression was expressed as the decibel change in TEOAE magnitude obtained with versus without the presence of the broadband noise. TEOAE responses were also examined for middle ear muscle reflex activation and synchronous spontaneous otoacoustic emissions (SSOAEs). Speech-in-noise perception was assessed using the closed-set coordinate response measure word recognition task and the open-set Institute of Electrical and Electronics Engineers sentence task. Speech and noise were presented to right ears at two SNRs. Performance on each task was scored as percent correct. Associations between contralateral suppression and speech-in-noise performance were quantified using partial rank correlational analyses, controlling for the variables age and high-frequency pure-tone average. Results: One subject was excluded due to probable middle ear muscle reflex activation. Subjects showed a wide range of contralateral suppression values, consistent with previous reports. Three subjects with SSOAEs had similar contralateral suppression results as subjects without SSOAEs. The magnitude of contralateral suppression was not significantly correlated with speech-in-noise performance on either task at a single SNR ( p > 0.05), contrary to hypothesis. However, contralateral suppression was significantly correlated with the slope of the psychometric function, computed as the difference between performance levels at the two SNRs divided by 3 (decibel difference between the 2 SNRs) for the coordinate response measure task (partial r s = 0.59; p = 0.04) and for the Institute of Electrical and Electronics Engineers task (partial r s = 0.60; p = 0.03). Conclusions: In a group of primarily older adults with normal hearing or mild hearing loss, olivocochlear efferent activity assessed using contralateral suppression of TEOAEs was not associated with speech-in-noise performance at a single SNR. However, auditory efferent activity appears to be associated with the slope of the psychometric function for both a word and sentence recognition task in noise. Results suggest that individuals with stronger MOC efferent activity tend to be more responsive to changes in SNR, where small increases in SNR result in better speech-in-noise performance relative to individuals with weaker MOC efferent activity. Additionally, the results suggest that the slope of the psychometric function may be a more useful metric than performance at a single SNR when examining the relationship between speech recognition in noise and MOC efferent activity.

Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs. Auditory functional recovery was measured by serial auditory brainstem responses over a nine-week follow-up period, and HC regeneration was evaluated by immunohistological evaluations and scanning electron microscopy. Significant HC restoration and hearing recovery were observed across a broad tonotopic range in ears treated with siHes1 NPs, beginning at three weeks and extending out to nine weeks post-treatment. Moreover, both ectopic and immature HCs were uniquely observed in noise-injured cochleae treated with siHes1 NPs, consistent with de novo HC production. Our results indicate that durable cochlear HCs were regenerated and promoted significant hearing recovery in adult guinea pigs through reversible modulation of Hes1 expression. Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo.

Both mice and primates are used to model the human auditory system. The primate order possesses unique cortical specializations that govern auditory processing. Given the power of molecular and genetic tools available in the mouse model, it is essential to understand the similarities and differences in auditory cortical processing between mice and primates. To address this issue, we directly compared temporal encoding properties of neurons in the auditory cortex of awake mice and awake squirrel monkeys (SQMs). Stimuli were drawn from a sinusoidal amplitude modulation (SAM) paradigm, which has been used previously both to characterize temporal precision and to model the envelopes of natural sounds. Neural responses were analyzed with linear template-based decoders. In both species, spike timing information supported better modulation frequency discrimination than rate information, and multiunit responses generally supported more accurate discrimination than single-unit responses from the same site. However, cortical responses in SQMs supported better discrimination overall, reflecting superior temporal precision and greater rate modulation relative to the spontaneous baseline and suggesting that spiking activity in mouse cortex was less strictly regimented by incoming acoustic information. The quantitative differences we observed between SQM and mouse cortex support the idea that SQMs offer advantages for modeling precise responses to fast envelope dynamics relevant to human auditory processing. Nevertheless, our results indicate that cortical temporal processing is qualitatively similar in mice and SQMs and thus recommend the mouse model for mechanistic questions, such as development and circuit function, where its substantial methodological advantages can be exploited. NEW & NOTEWORTHY To understand the advantages of different model organisms, it is necessary to directly compare sensory responses across species. Contrasting temporal processing in auditory cortex of awake squirrel monkeys and mice, with parametrically matched amplitude-modulated tone stimuli, reveals a similar role of timing information in stimulus encoding. However, disparities in response precision and strength suggest that anatomical and biophysical differences between squirrel monkeys and mice produce quantitative but not qualitative differences in processing strategy.

Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc., had no hearing loss as measured by the auditory brainstem response (ABR) threshold at low-frequency range (<24 kHz). Here, we used multiple auditory function tests and re-examined hearing function in the Genentech Panx1 (Gen-Panx1) KO mouse. We found that ABR thresholds in the Gen-Panx1 KO mouse were significantly increased, in particular, in the high-frequency region. Moreover, consistent with the increase in ABR threshold, distortion product otoacoustic emission (DPOAE) and cochlear microphonics (CM), which reflect active cochlear amplification and auditory receptor current, respectively, were significantly reduced. These data demonstrated that the Gen-Panx1 KO mouse has hearing loss and further confirmed that Panx1 deficiency can cause deafness.

The vomeronasal system (VNS) is a major vertebrate chemosensory system that functions in parallel to the main olfactory system (MOS). Despite many similarities, the two systems dramatically differ in the temporal domain. While MOS responses are governed by breathing and follow a subsecond temporal scale, VNS responses are uncoupled from breathing and evolve over seconds. This suggests that the contribution of response dynamics to stimulus information will differ between these systems. While temporal dynamics in the MOS are widely investigated, similar analyses in the accessory olfactory bulb (AOB) are lacking. Here, we have addressed this issue using controlled stimulus delivery to the vomeronasal organ of male and female mice. We first analyzed the temporal properties of AOB projection neurons and demonstrated that neurons display prolonged, variable, and neuron-specific characteristics. We then analyzed various decoding schemes using AOB population responses. We showed that compared with the simplest scheme (i.e., integration of spike counts over the entire response period), the division of this period into smaller temporal bins actually yields poorer decoding accuracy. However, optimal classification accuracy can be achieved well before the end of the response period by integrating spike counts within temporally defined windows. Since VNS stimulus uptake is variable, we analyzed decoding using limited information about stimulus uptake time, and showed that with enough neurons, such time-invariant decoding is feasible. Finally, we conducted simulations that demonstrated that, unlike the main olfactory bulb, the temporal features of AOB neurons disfavor decoding with high temporal accuracy, and, rather, support decoding without precise knowledge of stimulus uptake time. SIGNIFICANCE STATEMENT A key goal in sensory system research is to identify which metrics of neuronal activity are relevant for decoding stimulus features. Here, we describe the first systematic analysis of temporal coding in the vomeronasal system (VNS), a chemosensory system devoted to socially relevant cues. Compared with the main olfactory system, timescales of VNS function are inherently slower and variable. Using various analyses of real and simulated data, we show that the consideration of response times relative to stimulus uptake can aid the decoding of stimulus information from neuronal activity. However, response properties of accessory olfactory bulb neurons favor decoding schemes that do not rely on the precise timing of stimulus uptake. Such schemes are consistent with the variable nature of VNS stimulus uptake.

Sleep-wake history, wake behaviors, lighting conditions, and circadian time influence sleep, but neither their relative contribution nor the underlying mechanisms are fully understood. The dynamics of electroencephalogram (EEG) slow-wave activity (SWA) during sleep can be described using the two-process model, whereby the parameters of homeostatic Process S are estimated using empirical EEG SWA (0.5-4 Hz) in nonrapid eye movement sleep (NREMS), and the 24 hr distribution of vigilance states. We hypothesized that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behavior, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREMS SWA derived from continuous EEG recordings from the frontal and occipital cortex in mice. The animals showed prolonged wake periods, followed by consolidated sleep, both during the dark and light phases, and wakefulness primarily consisted of voluntary wheel running, learning a new motor skill or novel object exploration. Simulated SWA matched empirical levels well across conditions, and neither waking experience nor time of day had a significant influence on the fit between data and simulation. However, we consistently observed that Process S declined during sleep significantly faster in the frontal than in the occipital area of the neocortex. The striking resilience of the model to specific wake behaviors, lighting conditions, and time of day suggests that intrinsic factors underpinning the dynamics of Process S are robust to extrinsic influences, despite their major role in shaping the overall amount and distribution of vigilance states across 24 hr.

The Mongolian gerbil (Meriones unguiculatus) is widely used as a model organism for the human auditory system. Its hearing range is very similar to ours and it uses the same mechanisms for sound localization. The auditory circuits underlying these functions have been characterized. However, important mechanistic details are still under debate. To elucidate these issues, precise and reversible optogenetic manipulation of neuronal activity in this complex circuitry is required. However, genetic and genomic resources for the Mongolian gerbil are poorly developed. Here, we demonstrate a reliable gene delivery system using an AAV8(Y337F)-pseudotyped recombinant adeno-associated virus (AAV) 2-based vector in which the pan-neural human synapsin (hSyn) promoter drives neuron-specific expression of CatCH (Ca2+-permeable channelrhodopsin) or NpHR3.0 (Natronomonas pharaonis halorhodopsin). After stereotactic injection into the gerbil's auditory brainstem (medial nucleus of the trapezoid body, dorsal nucleus of the lateral lemniscus) and midbrain [inferior colliculus (IC)], we characterized CatCH- and/or NpHR3.0-transduced neurons in acute brain slices by means of whole-cell patch-clamp recordings. As the response properties of optogenetic tools strongly depend on neuronal biophysics, this parameterization is crucial for their in vivo application. In a proof-of-principle experiment in anesthetized gerbils, we observed strong suppression of sound-evoked neural responses in the dorsal nucleus of the lateral lemniscus (DNLL) and IC upon light activation of NpHR3.0. The successful validation of gene delivery and optogenetic tools in the Mongolian gerbil paves the way for future studies of the auditory circuits in this model system.

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Spikes (action potential) responses of most primary visual cortical cells in the macaque are sharply tuned for the orientation of a line or an edge and neurons preferring similar orientations are clustered together in cortical columns. The preferred stimulus orientation of these columns span the full range of orientations, as observed in recordings of spikes, which represent the outputs of cortical neurons. However, when we imaged also the thalamic input to these cells that occur on a larger spatial scale, we found that the orientation domain map of the primary visual cortex did not show the diversity of orientations exhibited by signals representing outputs of the cells. This map was dominated by just the one orientation that is most commonly represented in subcortical responses. This supports cortical feature selectivity and columnar architecture being built upon feed-forward signals transmitted from the thalamus in a very limited number of broadly-tuned input channels.

Making perceptual decisions to categorize unknown sensory stimuli is a fundamental cognitive function, known as category learning. The posterior parietal cortex (PPC), although has been intensively studied for its role in decision-making and other cognitive functions, its causal link with behavior remains controversial. Here we combine in vivo two-photon imaging, circuit manipulation and auditory psychophysics behavior in mice to probe the role of PPC and its connectivity with sensory cortex in decision-making during category learning. We show that PPC neuronal populations exhibit coding dynamics characteristic of category learning, showing representations for both new sensory stimuli and prior learned categories. Circuit-specific perturbations of PPC and its projections to auditory cortex impaired decision performance specifically for categorizing new auditory stimuli. These data reveal a dynamic and causal role of the parietal-auditory circuit in decision-making, integrating prior knowledge to guide categorical decisions on new sensory stimuli.

Cross-frequency coupling in the hippocampus has been hypothesized to support higher-cognition functions. While gamma modulation by theta is widely accepted, evidence of phase-coupling between the two frequency components is so far unconvincing. Our observations show that theta and gamma energy increases with rat speed, while the overall nonlinearity of the LFP trace also increases, suggesting that energy flow is fundamental for hippocampal dynamics. This contradicts current representations based on the Kuramoto phase model. Therefore, we propose a new approach, based on the three-wave equation, a universally-valid nonlinear-physics paradigm that synthesizes the effects of leading order, quadratic nonlinearity. The paradigm identifies bispectral analysis as the natural tool for investigating LFP cross-frequency coupling. Our results confirm the effectiveness of the approach by showing unambiguous coupling between theta and gamma. Bispectra features agree with predictions of the three-wave model, supporting the conclusion that cross-frequency coupling is a manifestation of nonlinear energy transfers.

The ability to discriminate changes in the fine structure of complex sounds is well developed in birds. However, the precise limit of this discrimination ability and how it is used in the context of natural communication remains unclear. Here we describe natural variability in acoustic fine structure of male and female zebra finch calls. Results from psychoacoustic experiments demonstrate that zebra finches are able to discriminate extremely small differences in fine structure, which are on the order of the variation in acoustic fine structure that is present in their vocal signals. Results from signal analysis methods also suggest that acoustic fine structure may carry information that distinguishes between biologically relevant categories including sex, call type and individual identity. Combined, our results are consistent with the hypothesis that zebra finches can encode biologically relevant information within the fine structure of their calls. This study provides a foundation for our understanding of how acoustic fine structure may be involved in animal communication.

Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties. Here we conducted in vivo and in vitro recordings in the mouse LGN, beginning just after natural eye opening, to determine how receptive fields develop as excitatory and feedforward inhibitory retinal afferents refine. Experiments used both male and female subjects. For in vivo assessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields at eye-opening were >2 times larger than in adulthood, and decreased in size over the subsequent week. This topographic refinement was accompanied by other spatial changes, such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. We performed in vitro recordings of the synaptic responses evoked by optic tract stimulation across the same time period. These recordings revealed a pairing of decreased excitatory and increased feedforward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement. SIGNIFICANCE STATEMENT The development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity-dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in the lateral geniculate nucleus (LGN) to the remodeling of retinal and inhibitory feedforward convergence onto LGN neurons. These findings should thus provide a starting point for testing the cell type-specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and for determining the effect of these mechanisms on the establishment of mature receptive fields in the LGN.