Subthreshold Responses Research Articles

A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events.

A remaining challenge for genetically encoded voltage indicators (GEVIs) is the reliable detection of excitatory postsynaptic potentials (EPSPs). Here, we developed ASAP5 as a GEVI with enhanced activation kinetics and responsivity near resting membrane potentials for improved detection of both spiking and subthreshold activity. ASAP5 reported action potentials (APs) invivo with higher signal-to-noise ratios than previous GEVIs and successfully detected graded and subthreshold responses to sensory stimuli in single two-photon trials. In cultured rat or human neurons, somatic ASAP5 reported synaptic events propagating centripetally and could detect ∼1-mV EPSPs. By imaging spontaneous EPSPs throughout dendrites, we found that EPSP amplitudes decay exponentially during propagation and that amplitude at the initiation site generally increases with distance from the soma. These results extend the applications of voltage imaging to the quantal response domain, including in human neurons, opening up the possibility of high-throughput, high-content characterization of neuronal dysfunction in disease.

Corticomotor pathway function and recovery after stroke: a look back and a way forward.

Stroke is a leading cause of adult disability that results in motor deficits and reduced independence. Regaining independence relies on motor recovery, particularly regaining function of the hand and arm. This review presents evidence from human studies that have used transcranial magnetic stimulation (TMS) to identify neurophysiological mechanisms underlying upper limb motor recovery early after stroke. TMS studies undertaken at the subacute stage after stroke have identified several neurophysiological factors that can drive motor impairment, including membrane excitability, the recruitment of corticomotor neurons, and glutamatergic and GABAergic neurotransmission. However, the inherent variability and subsequent poor reliability of measures derived from motor evoked potentials (MEPs) limit the use of TMS for prognosis at the individual patient level. Currently, prediction tools that provide the most accurate information about upper limb motor outcomes for individual patients early after stroke combine clinical measures with a simple neurophysiological biomarker based on MEP presence or absence, i.e. MEP status. Here, we propose a new compositional framework to examine MEPs across several upper limb muscles within a threshold matrix. The matrix can provide a more comprehensive view of corticomotor function and recovery after stroke by quantifying the evolution of subthreshold and suprathreshold MEPs through compositional analyses. Our contention is that subthreshold responses might be the most sensitive to reduced output of corticomotor neurons, desynchronized firing of the remaining neurons, and myelination processes that occur early after stroke. Quantifying subthreshold responses might provide new insights into post-stroke neurophysiology and improve the accuracy of prediction of upper limb motor outcomes.

Associative Learning of Quantitative Mechanosensory Stimuli in Honeybees.

The proboscis extension response (PER) has been widely used to evaluate honeybees' (Apis mellifera) learning and memory abilities, typically by using odors and visual cues for the conditioned stimuli. Here we asked whether honeybees could learn to distinguish between different magnitudes of the same type of stimulus, given as two speeds of air flux. By taking advantage of a novel automated system for administering PER experiments, we determined that the bees were highly successful when the lower air flux was rewarded and less successful when the higher flux was rewarded. Importantly, since our method includes AI-assisted analysis, we were able to consider subthreshold responses at a high temporal resolution; this analysis revealed patterns of rapid generalization and slowly acquired discrimination between the rewarded and unrewarded stimuli, as well as indications that the high air flux may have been mildly aversive. The learning curve for these mechanosensory stimuli, at least when the lower flux is rewarded, more closely mimics prior data from olfactory PER studies rather than visual ones, possibly in agreement with recent findings that the insect olfactory system is also sensitive to mechanosensory information. This work demonstrates a new modality to be used in PER experiments and lays the foundation for deeper exploration of honeybee cognitive processes when posed with complex learning challenges.

Integrate-and-fire-type models of the lateral superior olive.

Neurons of the lateral superior olive (LSO) in the auditory brainstem play a fundamental role in binaural sound localization. Previous theoretical studies developed various types of neuronal models to study the physiological functions of the LSO. These models were usually tuned to a small set of physiological data with specific aims in mind. Therefore, it is unclear whether and how they can be related to each other, how widely applicable they are, and which model is suitable for what purposes. In this study, we address these questions for six different single-compartment integrate-and-fire (IF) type LSO models. The models are divided into two groups depending on their subthreshold responses: passive (linear) models with only the leak conductance and active (nonlinear) models with an additional low-voltage-activated potassium conductance that is prevalent among the auditory system. Each of these two groups is further subdivided into three subtypes according to the spike generation mechanism: one with simple threshold-crossing detection and voltage reset, one with threshold-crossing detection plus a current to mimic spike shapes, and one with a depolarizing exponential current for spiking. In our simulations, all six models were driven by identical synaptic inputs and calibrated with common criteria for binaural tuning. The resulting spike rates of the passive models were higher for intensive inputs and lower for temporally structured inputs than those of the active models, confirming the active function of the potassium current. Within each passive or active group, the simulated responses resembled each other, regardless of the spike generation types. These results, in combination with the analysis of computational costs, indicate that an active IF model is more suitable than a passive model for accurately reproducing temporal coding of LSO. The simulation of realistic spike shapes with an extended spiking mechanism added relatively small computational costs.

Reliability of a TMS-derived threshold matrix of corticomotor function.

Transcranial magnetic stimulation (TMS) studies typically focus on suprathreshold motor evoked potentials (MEPs), overlooking small MEPs representing subthreshold corticomotor pathway activation. Assessing subthreshold excitability could provide insights into corticomotor pathway integrity and function, particularly in neurological conditions like stroke. The aim of the study wasto examine the test-retest reliability of metrics derived from a novel compositional analysis of MEP data from older adults. The study also compared the composition between the dominant (D) and non-dominant (ND) sides and explored the association between subthreshold responses and resting motor threshold. In this proof-of-concept study, 23 healthy older adults participated in two identical experimental sessions. Stimulus-response (S-R) curves and threshold matrices were constructed using single-pulse TMS across intensities to obtain MEPs in four upper limb muscles. S-R curves had reliable slopes for every muscle (Intraclass Correlation Coefficient range = 0.58-0.88). Subliminal and suprathreshold elements of the threshold matrix showed good-excellent reliability (D subliminal ICC = 0.83; ND subliminal ICC = 0.79; D suprathreshold ICC = 0.92; ND suprathreshold ICC = 0.94). By contrast, subthreshold elements of the matrix showed poor reliability, presumably due to a floor effect (D subthreshold ICC = 0.39; ND subthreshold ICC = 0.05). No composition differences were found between D and ND sides (suprathreshold BF01 = 3.85; subthreshold BF01 = 1.68; subliminal BF01 = 3.49). The threshold matrix reliably assesses subliminal and suprathreshold MEPs in older adults. Further studies are warranted to evaluate the utility of compositional analyses for assessing recovery of corticomotor pathway function after neurological injury.

Somatic Integration of Incoherent Dendritic Inputs in the Gerbil Medial Superior Olive.

The medial superior olive (MSO) is a binaural nucleus that is specialized in detecting the relative arrival times of sounds at both ears. Excitatory inputs to its neurons originating from either ear are segregated to different dendrites. To study the integration of synaptic inputs both within and between dendrites, we made juxtacellular and whole-cell recordings from the MSO in anesthetized female gerbils, while presenting a "double zwuis" stimulus, in which each ear received its own set of tones, which were chosen in a way that all second-order distortion products (DP2s) could be uniquely identified. MSO neurons phase-locked to multiple tones within the multitone stimulus, and vector strength, a measure for spike phase-locking, generally depended linearly on the size of the average subthreshold response to a tone. Subthreshold responses to tones in one ear depended little on the presence of sound in the other ear, suggesting that inputs from different ears sum linearly without a substantial role for somatic inhibition. The "double zwuis" stimulus also evoked response components in the MSO neuron that were phase-locked to DP2s. Bidendritic subthreshold DP2s were quite rare compared with bidendritic suprathreshold DP2s. We observed that in a small subset of cells, the ability to trigger spikes differed substantially between both ears, which might be explained by a dendritic axonal origin. Some neurons that were driven monaurally by only one of the two ears nevertheless showed decent binaural tuning. We conclude that MSO neurons are remarkably good in finding binaural coincidences even among uncorrelated inputs.SIGNIFICANCE STATEMENT Neurons in the medial superior olive are essential for precisely localizing low-frequency sounds in the horizontal plane. From their soma, only two dendrites emerge, which are innervated by inputs originating from different ears. Using a new sound stimulus, we studied the integration of inputs both within and between these dendrites in unprecedented detail. We found evidence that inputs from different dendrites add linearly at the soma, but that small increases in somatic potentials could lead to large increases in the probability of generating a spike. This basic scheme allowed the MSO neurons to detect the relative arrival time of inputs at both dendrites remarkably efficient, although the relative size of these inputs could differ considerably.

Comparative Effects of Domain-Specific Human Monoclonal Antibodies Against LGI1 on Neuronal Excitability.

Autoantibodies to leucine-rich glioma inactivated protein 1 (LGI1) cause an autoimmune limbic encephalitis with frequent focal seizures and anterograde memory dysfunction. LGI1 is a neuronal secreted linker protein with 2 functional domains: the leucine-rich repeat (LRR) and epitempin (EPTP) regions. LGI1 autoantibodies are known to interfere with presynaptic function and neuronal excitability; however, their epitope-specific mechanisms are incompletely understood. We used patient-derived monoclonal autoantibodies (mAbs), which target either LRR or EPTP domains of LGI1 to investigate long-term antibody-induced alteration of neuronal function. LRR- and EPTP-specific effects were evaluated by patch-clamp recordings in cultured hippocampal neurons and compared with biophysical neuron modeling. Kv1.1 channel clustering at the axon initial segment (AIS) was quantified by immunocytochemistry and structured illumination microscopy techniques. Both EPTP and LRR domain-specific mAbs decreased the latency of first somatic action potential firing. However, only the LRR-specific mAbs increased the number of action potential firing together with enhanced initial instantaneous frequency and promoted spike-frequency adaptation, which were less pronounced after the EPTP mAb. This also led to an effective reduction in the slope of ramp-like depolarization in the subthreshold response, suggesting Kv1 channel dysfunction. A biophysical model of a hippocampal neuron corroborated experimental results and suggests that an isolated reduction of the conductance of Kv1-mediated K+ currents largely accounts for the antibody-induced alterations in the initial firing phase and spike-frequency adaptation. Furthermore, Kv1.1 channel density was spatially redistributed from the distal toward the proximal site of AIS under LRR mAb treatment and, to a lesser extant, under EPTP mAb. These findings indicate an epitope-specific pathophysiology of LGI1 autoantibodies. The pronounced neuronal hyperexcitability and SFA together with dropped slope of ramp-like depolarization after LRR-targeted interference suggest disruption of LGI1-dependent clustering of K+ channel complexes. Moreover, considering the effective triggering of action potentials at the distal AIS, the altered spatial distribution of Kv1.1 channel density may contribute to these effects through impairing neuronal control of action potential initiation and synaptic integration.

Near-additive temporal dynamics of sub-threshold population responses in macaque V1

Near-additive temporal dynamics of sub-threshold population responses in macaque V1

Ionic and morphological contributions to the variable gain of membrane responses in layer 2/3 pyramidal neurons of mouse primary visual cortex.

Many neuronal cell types exhibit a sliding scale of neuronal excitability in the subthreshold voltage range. This is due to a variable contribution of different voltage-gated ion channels, leading to scaling of input resistance (RN) as a function of membrane potential (Vm) and a voltage-dependent dynamic gain of neuronal responsiveness. In layer 2/3 pyramidal neurons within the primary visual cortex (V1), this response influences sensory processing by tightening neuronal tuning to preferred orientations, but the identity of the ionic conductances involved remains unknown. Here, we used in vitro physiological recordings in acute slices to identify the contributions of several voltage-dependent conductances to the dynamic gain of membrane responses in layer 2/3 pyramidal neurons in mouse primary visual cortex. We found that the steep voltage dependence of input resistance in these cells was mediated in part by a combination of persistent sodium, inwardly rectifying potassium, and hyperpolarization-activated nonselective cation channels. In addition, the steepness of the slope of the RN/Vm relationship was inversely correlated with the number of branches on the proximal apical dendrite. These data have uncovered physiological and morphological factors that underlie the scaling of membrane responses in L2/3 neurons of rodent V1. Regulation of these channels would serve as a mechanism of real-time neuromodulation of neuronal processing of sensory information.NEW & NOTEWORTHY Layer 2/3 pyramidal neurons in primary visual cortex scale subthreshold voltage responses with resting membrane potential because RN increases as Vm is depolarized. Here, we uncovered the voltage-dependent contributions of NaP, Kir, and HCN conductances toward this behavior, and we additionally demonstrated that the strength of the RN/Vm relationship is inversely correlated with proximal branching along the apical dendrite.

Activating parvalbumin-expressing interneurons produces iceberg effects in mouse primary visual cortex neurons

In the primary visual cortex (V1) inhibitory interneurons form a local circuit with excitatory pyramidal cells to produce distinct receptive field properties. Parvalbumin-expressing interneurons (Pvalb+) are the most common subclass of V1 interneurons, and studies of orientation tuning indicate they shape pyramidal stimulus selectivity by balancing excitation with inhibition relative to the spike threshold. The iceberg effect, where subthreshold responses have broader tuning than spiking responses, predicts that other receptive field properties besides orientation tuning should also be affected by this balance mediated by Pvalb+ cells. To test this, we measured receptive field size and visual latency of pyramidal cells while Pvalb+ activity was optogenetically increased. We found that amplifying Pvalb+ input to pyramidal cells significantly increased their latency and decreased their receptive field size, which corroborates the proposed role of Pvalb+ interneurons in sculpting pyramidal tuning by controlling cortical gain.

Ultra-Low Threshold Voltage OFET Using PANI Nanofibers

Organic field-effect transistors (OFETs) have shown potential market in many low-power sensing applications. Toward that, the fabrication of sharp on/off OFET is essential. Herein, we present an attempt to fabricate OFET using polyaniline (PANI), in the form of PANI-nanofibers with a fiber diameter of 75 nm, as an active semiconductor layer. The polymethyl methacrylate (PMMA) is utilized as a gate dielectric with an aluminum bottom electrode. Top electrodes for both source and drain were fabricated of gold. The Primary, in-situ polymerization method is used in preparing the PANI as a semiconductor film. The morphological and optical properties of PANI nanofibers, as well as PMMA oxide thin-film, were investigated using SEM, FTIR, AFM, and UV-Vis. Spectrometer. The bandgap energy was observed to be 2.2 eV. Consequently, the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</i> characteristics were studied for the device, showing a sharp sub-threshold response. An ultra-low threshold voltage of 0.17 V was recorded, promoting the fabricated devices for various sensing applications.

Investigation of Neuron Latency Modulated by Bilateral Inferior Collicular Interactions Using Whole-Cell Patch Clamp Recording in Brain Slices.

As the final level of the binaural integration center in the subcortical nucleus, the inferior colliculus (IC) plays an essential role in receiving binaural information input. Previous studies have focused on how interactions between the bilateral IC affect the firing rate of IC neurons. However, little is known concerning how the interactions within the bilateral IC affect neuron latency. In this study, we explored the synaptic mechanism of the effect of bilateral IC interactions on the latency of IC neurons. We used whole-cell patch clamp recordings to assess synaptic responses in isolated brain slices of Kunming mice. The results demonstrated that the excitation-inhibition projection was the main projection between the bilateral IC. Also, the bilateral IC interactions could change the reaction latency of most neurons to different degrees. The variation in latency was related to the type of synaptic input and the relative intensity of the excitation and inhibition. Furthermore, the latency variation also was caused by the duration change of the first subthreshold depolarization firing response of the neurons. The distribution characteristics of the different types of synaptic input also differed. Excitatory-inhibitory neurons were widely distributed in the IC dorsal and central nuclei, while excitatory neurons were relatively concentrated in these two nuclei. Inhibitory neurons did not exhibit any apparent distribution trend due to the small number of assessed neurons. These results provided an experimental reference to reveal the modulatory functions of bilateral IC projections.

P.0376 Subthreshold manic symptoms (sleep disturbance and irritability) and response to lurasidone in children and adolescents with bipolar depression

P.0376 Subthreshold manic symptoms (sleep disturbance and irritability) and response to lurasidone in children and adolescents with bipolar depression

Neocortex saves energy by reducing coding precision during food scarcity

SummaryInformation processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy use are regulated during food scarcity. Using whole-cell recordings and two-photon imaging in layer 2/3 mouse visual cortex, we found that food restriction reduced AMPA receptor conductance, reducing synaptic ATP use by 29%. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting potential. Consequently, neurons spiked at similar rates as controls but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost because it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening of orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. Our findings reveal that metabolic state dynamically regulates the energy spent on coding precision in neocortex.

Stimulus Feature-Specific Control of Layer 2/3 Subthreshold Whisker Responses by Layer 4 in the Mouse Primary Somatosensory Cortex.

In the barrel field of the rodent primary somatosensory cortex (S1bf), excitatory cells in layer 2/3 (L2/3) display sparse firing but reliable subthreshold response during whisker stimulation. Subthreshold responses encode specific features of the sensory stimulus, for example, the direction of whisker deflection. According to the canonical model for the flow of sensory information across cortical layers, activity in L2/3 is driven by layer 4 (L4). However, L2/3 cells receive excitatory inputs from other regions, raising the possibility that L4 partially drives L2/3 during whisker stimulation. To test this hypothesis, we combined patch-clamp recordings from L2/3 pyramidal neurons in S1bf with selective optogenetic inhibition of L4 during passive whisker stimulation in both anesthetized and awake head-restrained mice. We found that L4 optogenetic inhibition did not abolish the subthreshold whisker-evoked response nor it affected spontaneous membrane potential fluctuations of L2/3 neurons. However, L4 optogenetic inhibition decreased L2/3 subthreshold responses to whisker deflections in the preferred direction, and it increased L2/3 responses to stimuli in the nonpreferred direction, leading to a change in the direction tuning. Our results contribute to reveal the circuit mechanisms underlying the processing of sensory information in the rodent S1bf.

US EPA: Is there room to open a new window for evaluating potential sub-threshold effects and ecological risks?

With a rule published on 6 January 2021, the US Environmental Protection Agency (EPA) considers for the first time sub-threshold responses, abandoning the use of default dose-response models. This may affect worldwide scientific research, in terms of research design and methodology, and regulatory actions in China and other countries.

In Vivo Plasticity at Hippocampal Schaffer Collateral-CA1 Synapses: Replicability of the LTP Response and Pharmacology in the Long-Evans Rat.

Broad issues associated with non-replicability have been described in experimental pharmacological and behavioral cognitive studies. Efforts to prevent biases that contribute to non-replicable scientific protocols and to improve experimental rigor for reproducibility are increasingly seen as a basic requirement for the integrity of scientific research. Synaptic plasticity, encompassing long-term potentiation (LTP), is believed to underlie mechanisms of learning and memory. The present study was undertaken in Long-Evans (LE) rats, a strain of rat commonly used in cognitive behavioral tests, to (1) compare three LTP tetanisation protocols, namely, the high-frequency stimulation (HFS), the theta-burst stimulation (TBS), and the paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 stratum radiatum synapse and to (2) assess sensitivity to acute pharmacology. Results: (1) When compared to Sprague-Dawley (SD) rats, the HFS using a stimulus intensity of 50% of the maximum slope obtained from input/output (I/O) curves elicited lower and higher thresholds of synaptic plasticity responses in SD and LE rats, respectively. The 2-train TBS protocol significantly enhanced the LTP response in LE rats over the 5- and 10-train TBS protocols in both strains, and the 5 × TBS protocol inducing a subthreshold LTP response was used in subsequent pharmacological studies in LE rats. The PPF protocol, investigating the locus of the LTP response, showed no difference for the selected interstimulus intervals. (2) Scopolamine, a nonspecific muscarinic antagonist, had a subtle effect, whereas donepezil, an acetylcholinesterase inhibitor, significantly enhanced the LTP response, demonstrating the sensitivity of the TBS protocol to enhanced cholinergic tone. MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, significantly reduced LTP response, while memantine, another NMDA antagonist, had no effect on LTP response, likely associated with a weaker TBS protocol. PQ10, a phosphodiesterase-10 inhibitor, significantly enhanced the TBS-induced LTP response, but did not change the PPF response. Overall, the results confirm the strain-dependent differences in the form of synaptic plasticity, replicate earlier plasticity results, and report effective protocols that generate a relatively subthreshold margin of LTP induction and maintenance, which are suitable for pharmacology in the LE rat strain mainly used in cognitive studies.

Synaptic and intrinsic mechanisms underlying development of cortical direction selectivity.

Modifications of synaptic inputs and cell-intrinsic properties both contribute to neuronal plasticity and development. To better understand these mechanisms, we undertook an intracellular analysis of the development of direction selectivity in the ferret visual cortex, which occurs rapidly over a few days after eye opening. We found strong evidence of developmental changes in linear spatiotemporal receptive fields of simple cells, implying alterations in circuit inputs. Further, this receptive field plasticity was accompanied by increases in near-spike-threshold excitability and input-output gain that resulted in dramatically increased spiking responses in the experienced state. Increases in subthreshold membrane responses induced by the receptive field plasticity and the increased input-output spiking gain were both necessary to explain the elevated firing rates in experienced ferrets. These results demonstrate that cortical direction selectivity develops through a combination of plasticity in inputs and in cell-intrinsic properties.

Paradoxically Sparse Chemosensory Tuning in Broadly Integrating External Granule Cells in the Mouse Accessory Olfactory Bulb.

The accessory olfactory bulb (AOB), the first neural circuit in the mouse accessory olfactory system, is critical for interpreting social chemosignals. Despite its importance, AOB information processing is poorly understood compared with the main olfactory bulb (MOB). Here, we sought to fill gaps in the understanding of AOB interneuron function. We used 2-photon GCaMP6f Ca2+ imaging in an ex vivo preparation to study chemosensory tuning in AOB external granule cells (EGCs), interneurons hypothesized to broadly inhibit activity in excitatory mitral cells (MCs). In ex vivo preparations from mice of both sexes, we measured MC and EGC tuning to natural chemosignal blends and monomolecular ligands, finding that EGC tuning was sparser, not broader, than upstream MCs. Simultaneous electrophysiological recording and Ca2+ imaging showed no differences in GCaMP6f-to-spiking relationships in these cell types during simulated sensory stimulation, suggesting that measured EGC sparseness was not due to cell type-dependent variability in GCaMP6f performance. Ex vivo patch-clamp recordings revealed that EGC subthreshold responsivity was far broader than indicated by GCaMP6f Ca2+ imaging, and that monomolecular ligands rarely elicited EGC spiking. These results indicate that EGCs are selectively engaged by chemosensory blends, suggesting different roles for EGCs than analogous interneurons in the MOB.SIGNIFICANCE STATEMENT The mouse accessory olfactory system (AOS) interprets social chemosignals, but we poorly understand AOS information processing. Here, we investigate the functional properties of external granule cells (EGCs), a major class of interneurons in the accessory olfactory bulb (AOB). We hypothesized that EGCs, which are densely innervated by excitatory mitral cells (MCs), would show broad chemosensory tuning, suggesting a role in divisive normalization. Using ex vivo GCaMP6f imaging, we found that EGCs were instead more sparsely tuned than MCs. This was not due to weaker GCaMP6f signaling in EGCs than in MCs. Instead, we found that many MC-activating chemosignals caused only subthreshold EGC responses. This indicates a different role for AOB EGCs compared with analogous cells in the main olfactory bulb.

In vivo whole-cell recordings of stimulus-specific adaptation in the inferior colliculus

The inferior colliculus is an auditory structure where inputs from multiple lower centers converge, allowing the emergence of complex coding properties of auditory information such as stimulus-specific adaptation. Stimulus-specific adaptation is the adaptation of neuronal responses to a specific repeated stimulus, which does not entirely generalize to other new stimuli. This phenomenon provides a mechanism to emphasize saliency and potentially informative sensory inputs. Stimulus-specific adaptation has been traditionally studied analyzing the somatic spiking output. However, studies that correlate within the same inferior colliculus neurons their intrinsic properties, subthreshold responses and the level of acoustic stimulus-specific adaptation are still pending. For this, we recorded in vivo whole-cell patch-clamp neurons in the mouse inferior colliculus while stimulating with current injections or the classic auditory oddball paradigm.Our data based on cases of ten neuron, suggest that although passive properties were similar, intrinsic properties differed between adapting and non-adapting neurons. Non-adapting neurons showed a sustained-regular firing pattern that corresponded to central nucleus neurons and adapting neurons at the inferior colliculus cortices showed variable firing patterns. Our current results suggest that synaptic stimulus-specific adaptation was variable and could not be used to predict the presence of spiking stimulus-specific adaptation. We also observed a small trend towards hyperpolarized membrane potentials in adapting neurons and increased synaptic inhibition with consecutive stimulus repetitions in all neurons. This finding indicates a more simple type of adaptation, potentially related to potassium conductances. Hence, these data represent a modest first step in the intracellular study of stimulus-specific adaptation in inferior colliculus neurons in vivo that will need to be expanded with pharmacological manipulations to disentangle specific ionic channels participation.