International Journal of Nanomedicine · May 2012
Verena Scheper, Meyer, Stöver, … Lenarz
Abstract
Objective: Sensorineural hearing loss leads to the progressive degeneration of spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which should be suppressed to assure a close nerve-electrode interaction, the density of healthy SGC is one factor that influences the efficiency of cochlear implants (CI), the choice of treatment for affected patients. Rolipram, a phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory effects and might also reduce SGC degeneration and fibrosis, but it has to pass the cellular membrane to be biologically active. Methods: Lipidic nanocapsules (LNC) can be used as biodegradable drug carriers to increase the efficacy of conventional application methods. We examined the biological effects of rolipram and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor necrosis factor-α (TNF-α) production in vitro and on SGC survival in systemically-deafened guinea pigs in vivo. Results: Our results prove that rolipram does not have a beneficial effect on cultured SGC. Incorporation of rolipram in LNC increased the survival of SGC significantly. In the DC study, rolipram significantly inhibited TNF-α in a dose-dependent manner. The rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo data do not confirm the in vitro results. Conclusion: By transporting rolipram into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in vitro, but not in vivo. This might be due to dilution of test substances by perilymph or an inadequate release of rolipram based on differing in vivo and in vitro conditions. Nevertheless, based on in vitro results, proving a significantly increased neuronal survival when using LNC-rolipram compared to pure rolipram and pure LNC application, we believe that the combination of rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after CI implantation. We conclude that rolipram is a promising drug that can be used in inner ear therapy and that LNC have potential as an inner ear drug-delivery system. Further experiments with modified conditions might reveal in vivo biological effects.
Ear & Hearing · May 2012
Kelly C. Harris, Sara Wilson, Mark A. Eckert, Judy R. Dubno
Abstract
Objectives: The goal of this study was to examine the degree to which age-related differences in early or automatic levels of auditory processing and attention-related processes explain age-related differences in auditory temporal processing. We hypothesized that age-related differences in attention and cognition compound age-related differences at automatic levels of processing, contributing to the robust age effects observed during challenging listening tasks. Design: We examined age-related and individual differences in cortical event-related potential (ERP) amplitudes and latencies, processing speed, and gap detection from 25 younger and 25 older adults with normal hearing. ERPs were elicited by brief silent periods (gaps) in an otherwise continuous broadband noise and were measured under two listening conditions, passive and active. During passive listening, participants ignored the stimulus and read quietly. During active listening, participants button pressed each time they detected a gap. Gap detection (percent detected) was calculated for each gap duration during active listening (3, 6, 9, 12, and 15 msec). Processing speed was assessed using the Purdue Pegboard Test and the Connections Test. Repeated measures analyses of variance assessed effects of age on gap detection, processing speed, and ERP amplitudes and latencies. An "attention modulation" construct was created using linear regression to examine the effects of attention while controlling for age-related differences in auditory processing. Pearson correlation analyses assessed the extent to which attention modulation, ERPs, and processing speed predicted behavioral gap detection. Results: Older adults had significantly poorer gap detection and slower processing speed than younger adults. Even after adjusting for poorer gap detection, the neurophysiological response to gap onset was atypical in older adults with reduced P2 amplitudes and virtually absent N2 responses. Moreover, individual differences in attention modulation of P2 response latencies and N2 amplitudes predicted gap detection and processing speed in older adults. That is, older adults with P2 latencies that decreased and N2 amplitudes that increased with active listening had faster processing speed and better gap detection than those older adults whose P2 latencies increased and N2 amplitudes decreased with attention. Conclusions: The results from the present study are broadly consistent with previous findings that older adults exhibit significantly poorer gap detection than younger adults in challenging tasks. Even after adjusting for poorer gap detection, older and younger adults showed robust differences in their electrophysiological responses to sound offset. Furthermore, the degree to which attention modulated the ERP was associated with individual variation in measures of processing speed and gap detection. Taken together, these results suggest an age-related deficit in early or automatic levels of auditory temporal processing and that some older adults may be less able to compensate for declines in processing by attending to the stimulus. These results extend our previous findings and support the hypothesis that age-related differences in cognitive or attention-related processing, including processing speed, contribute to an age-related decrease in gap detection.
PLoS ONE · Apr 2012
Alex León, Diego Elgueda, María A. Silva, … Paul H. Delano
Abstract
Background: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/principal findings: Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/significance: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea.
The Journal of Neuroscience · Apr 2012
Mark D. Morrissey, Geith Maal-Bared, Sinead Brady, Kaori Takehara-Nishiuchi
Abstract
Anatomical connectivity and single neuron coding suggest a segregation of information representation within lateral (LEC) and medial (MEC) portions of the entorhinal cortex, a brain region serving as the primary input/output of the hippocampus and maintaining widespread connections to many association cortices. The present study aimed to expand this idea by examining whether these two subregions differentially contribute to memory retrieval for an association between temporally discontiguous stimuli. We found that reversible inactivation of the LEC, but not the MEC, severely impaired the retrieval of the recently and remotely acquired memory in rat trace eyeblink conditioning, in which a stimulus-free interval was interposed between the conditioned and unconditioned stimulus. Conversely, inactivation of the LEC had no effect on retrieval in delay eyeblink conditioning, where two stimuli were presented without an interval. Therefore, the LEC, but not the MEC, plays a long-lasting role in the retrieval of a memory for an association between temporally discontiguous stimuli.
The Journal of Neuroscience · Apr 2012
Patrick McGillivray, Katrin Vonderschen, Eric S. Fortune, Maurice J. Chacron
Abstract
Natural stimuli often have time-varying first-order (i.e., mean) and second-order (i.e., variance) attributes that each carry critical information for perception and can vary independently over orders of magnitude. Experiments have shown that sensory systems continuously adapt their responses based on changes in each of these attributes. This adaptation creates ambiguity in the neural code as multiple stimuli may elicit the same neural response. While parallel processing of first- and second-order attributes by separate neural pathways is sufficient to remove this ambiguity, the existence of such pathways and the neural circuits that mediate their emergence have not been uncovered to date. We recorded the responses of midbrain electrosensory neurons in the weakly electric fish Apteronotus leptorhynchus to stimuli with first- and second-order attributes that varied independently in time. We found three distinct groups of midbrain neurons: the first group responded to both first- and second-order attributes, the second group responded selectively to first-order attributes, and the last group responded selectively to second-order attributes. In contrast, all afferent hindbrain neurons responded to both first- and second-order attributes. Using computational analyses, we show how inputs from a heterogeneous population of ON- and OFF-type afferent neurons are combined to give rise to response selectivity to either first- or second-order stimulus attributes in midbrain neurons. Our study thus uncovers, for the first time, generic and widely applicable mechanisms by which parallel processing of first- and second-order stimulus attributes emerges in the brain.
Ergonomics · Apr 2012
Elizabeth A. Felton, Justin C. Williams, Gregg C. Vanderheiden, Robert G. Radwin
Abstract
It is not well understood how people perceive the difficulty of performing brain-computer interface (BCI) tasks, which specific aspects of mental workload contribute the most, and whether there is a difference in perceived workload between participants who are able-bodied and disabled. This study evaluated mental workload using the NASA Task Load Index (TLX), a multi-dimensional rating procedure with six subscales: Mental Demands, Physical Demands, Temporal Demands, Performance, Effort, and Frustration. Able-bodied and motor disabled participants completed the survey after performing EEG-based BCI Fitts' law target acquisition and phrase spelling tasks. The NASA-TLX scores were similar for able-bodied and disabled participants. For example, overall workload scores (range 0-100) for 1D horizontal tasks were 48.5 (SD = 17.7) and 46.6 (SD 10.3), respectively. The TLX can be used to inform the design of BCIs that will have greater usability by evaluating subjective workload between BCI tasks, participant groups, and control modalities. Practitioner summary: Mental workload of brain-computer interfaces (BCI) can be evaluated with the NASA Task Load Index (TLX). The TLX is an effective tool for comparing subjective workload between BCI tasks, participant groups (able-bodied and disabled), and control modalities. The data can inform the design of BCIs that will have greater usability.
PLoS ONE · Apr 2012
Lei Han, Yonghai Zhang, Yunxiao Lou, Ying Xiong
Abstract
Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.
The Journal of Neuroscience · Apr 2012
Megumi Kaneko, Yuxiang Xie, Juan Ji An, … Baoji Xu
Abstract
Sensory experience in early postnatal life shapes neuronal connections in the brain. Here we report that the local synthesis of brain-derived neurotrophic factor (BDNF) in dendrites plays an important role in this process. We found that dendritic spines of layer 2/3 pyramidal neurons of the visual cortex in mutant mice lacking dendritic Bdnf mRNA and thus local BDNF synthesis were normal at 3 weeks of age, but thinner, longer, and more closely spaced (morphological features of immaturity) at 4 months of age than in wild-type (WT) littermates. Layer 2/3 of the visual cortex in these mutant animals also had fewer GABAergic presynaptic terminals at both ages. The overall size and shape of dendritic arbors were, however, similar in mutant and WT mice at both ages. By using optical imaging of intrinsic signals and single-unit recordings, we found that mutant animals failed to recover cortical responsiveness following monocular deprivation (MD) during the critical period, although they displayed normally the competitive loss of responsiveness to an eye briefly deprived of vision. Furthermore, MD still induced a loss of responsiveness to the closed eye in adult mutant mice, but not in adult WT mice. These results indicate that dendritic BDNF synthesis is required for spine pruning, late-phase spine maturation, and recovery of cortical responsiveness following sensory deprivation. They also suggest that maturation of dendritic spines is required for the maintenance of cortical responsiveness following sensory deprivation in adulthood.
Clinical Neurophysiology · Apr 2012
Itzel Orduña, Estella H. Liu, Barbara A. Church, … Eduardo Mercado
Abstract
Objective: Perceptual sensitivities are malleable via learning, even in adults. We trained adults to discriminate complex sounds (periodic, frequency-modulated sweep trains) using two different training procedures, and used psychoacoustic tests and evoked potential measures (the N1-P2 complex) to assess changes in both perceptual and neural sensitivities. Methods: Training took place either on a single day, or daily across eight days, and involved discrimination of pairs of stimuli using a single-interval, forced-choice task. In some participants, training started with dissimilar pairs that became progressively more similar across sessions, whereas in others training was constant, involving only one, highly similar, stimulus pair. Results: Participants were better able to discriminate the complex sounds after training, particularly after progressive training, and the evoked potentials elicited by some of the sounds increased in amplitude following training. Significant amplitude changes were restricted to the P2 peak. Conclusions: Our findings indicate that changes in perceptual sensitivities parallel enhanced neural processing. Significance: These results are consistent with the proposal that changes in perceptual abilities arise from the brain's capacity to adaptively modify cortical representations of sensory stimuli, and that different training regimens can lead to differences in cortical sensitivities, even after relatively short periods of training.
PLoS ONE · Mar 2012
Michele Bellesi, Vladyslav V. Vyazovskiy, Giulio Tononi, … Fiorenzo Conti
Abstract
The glutamate transporter GLT-1 is responsible for the largest proportion of total glutamate transport. Recently, it has been demonstrated that ceftriaxone (CEF) robustly increases GLT-1 expression. In addition, physiological studies have shown that GLT-1 up-regulation strongly affects synaptic plasticity, and leads to an impairment of the prepulse inhibition, a simple form of information processing, thus suggesting that GLT-1 over-expression may lead to dysfunctions of large populations of neurons. To test this possibility, we assessed whether CEF affects cortical electrical activity by using chronic electroencephalographic (EEG) recordings in male WKY rats. Spectral analysis showed that 8 days of CEF treatment resulted in a delayed reduction in EEG theta power (7-9 Hz) in both frontal and parietal derivations. This decrease peaked at day 10, i.e., 2 days after the end of treatment, and disappeared by day 16. In addition, we found that the same CEF treatment increased motor activity, especially when EEG changes are more prominent. Taken together, these data indicate that GLT-1 up-regulation, by modulating glutamatergic transmission, impairs the activity of widespread neural circuits. In addition, the increased motor activity and prepulse inhibition alterations previously described suggest that neural circuits involved in sensorimotor control are particularly sensitive to GLT-1 up-regulation.
PLoS ONE · Mar 2012
Daniela Neuhofer, Bernhard Ronacher
Abstract
Background: Animals that communicate by sound face the problem that the signals arriving at the receiver often are degraded and masked by noise. Frequency filters in the receiver's auditory system may improve the signal-to-noise ratio (SNR) by excluding parts of the spectrum which are not occupied by the species-specific signals. This solution, however, is hardly amenable to species that produce broad band signals or have ears with broad frequency tuning. In mammals auditory filters exist that work in the temporal domain of amplitude modulations (AM). Do insects also use this type of filtering? Principal findings: Combining behavioural and neurophysiological experiments we investigated whether AM filters may improve the recognition of masked communication signals in grasshoppers. The AM pattern of the sound, its envelope, is crucial for signal recognition in these animals. We degraded the species-specific song by adding random fluctuations to its envelope. Six noise bands were used that differed in their overlap with the spectral content of the song envelope. If AM filters contribute to reduced masking, signal recognition should depend on the degree of overlap between the song envelope spectrum and the noise spectra. Contrary to this prediction, the resistance against signal degradation was the same for five of six masker bands. Most remarkably, the band with the strongest frequency overlap to the natural song envelope (0-100 Hz) impaired acceptance of degraded signals the least. To assess the noise filter capacities of single auditory neurons, the changes of spike trains as a function of the masking level were assessed. Increasing levels of signal degradation in different frequency bands led to similar changes in the spike trains in most neurones. Conclusions: There is no indication that auditory neurones of grasshoppers are specialized to improve the SNR with respect to the pattern of amplitude modulations.
PLoS ONE · Mar 2012
David Pérez-González, Olga Hernández, Ellen Covey, Manuel S. Malmierca
Abstract
The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABA(A)-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABA(A) receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABA(A)-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron.
Journal of Comparative Physiology A · Mar 2012
M. Hartbauer, M. E. Siegert, I. Fertschai, H. Römer
Abstract
Acoustically communicating animals often have to cope with ambient noise that has the potential to interfere with the perception of conspecific signals. Here we use the synchronous display of mating signals in males of the tropical katydid Mecopoda elongata in order to assess the influence of nocturnal rainforest noise on signal perception. Loud background noise may disturb chorus synchrony either by masking the signals of males or by interaction of noisy events with the song oscillator. Phase-locked synchrony of males was studied under various signal-to-noise ratios (SNRs) using either native noise or the audio component of noise (<9 kHz). Synchronous entrainment was lost at a SNR of -3 dB when native noise was used, whereas with the audio component still 50% of chirp periods matched the pacer period at a SNR of -7 dB. Since the chirp period of solo singing males remained almost unaffected by noise, our results suggest that masking interference limits chorus synchrony by rendering conspecific signals ambiguous. Further, entrainment with periodic artificial signals indicates that synchrony is achieved by ignoring heterospecific signals and attending to a conspecific signal period. Additionally, the encoding of conspecific chirps was studied in an auditory neuron under the same background noise regimes.
Journal of Neural Engineering · Mar 2012
R A Normann, B R Dowden, M A Frankel, … G A Clark
Abstract
The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.
Ear & Hearing · Mar 2012
John H. Grose, Sara K. Mamo
Abstract
Objective: The purpose of this study was to determine the reliability of the electrophysiological binaural beat steady state response as a gauge of temporal fine structure coding, particularly as it relates to the aging auditory system. The hypothesis was that the response would be more robust in a lower, than in a higher, frequency region and in younger, than in older, adults. Design: Two experiments were undertaken. The first measured the 40 Hz binaural beat steady state response elicited by tone pairs in two frequency regions: lower (390 and 430 Hz tone pair) and higher (810 and 850 Hz tone pair). Frequency following responses (FFRs) evoked by the tones were also recorded. Ten young adults with normal hearing participated. The second experiment measured the binaural beat and FFRs in older adults but only in the lower frequency region. Fourteen older adults with relatively normal hearing participated. Response metrics in both experiments included response component signal-to-noise ratio (F statistic) and magnitude-squared coherence. Results: Experiment 1 showed that FFRs were elicited in both frequency regions but were more robust in the lower frequency region. Binaural beat responses elicited by the lower frequency pair of tones showed greater amplitude fluctuation within a participant than the respective FFRs. Experiment 2 showed that older adults exhibited similar FFRs to younger adults, but proportionally fewer older participants showed binaural beat responses. Age differences in onset responses were also observed. Conclusions: The lower prevalence of the binaural beat response in older adults, despite the presence of FFRs, provides tentative support for the sensitivity of this measure to age-related deficits in temporal processing. However, the lability of the binaural beat response advocates caution in its use as an objective measure of fine structure coding.
PLoS ONE · Feb 2012
Stephanie Kuhn, Neil Ingham, Selina Pearson, … Walter Marcotti
Abstract
Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+) currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca(2+) activated K(+) current (I(K,f)), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.
PLoS ONE · Feb 2012
Jozien B. M. Goense, Albert S. Feng
Abstract
Natural auditory scenes such as frog choruses consist of multiple sound sources (i.e., individual vocalizing males) producing sounds that overlap extensively in time and spectrum, often in the presence of other biotic and abiotic background noise. Detection of a signal in such environments is challenging, but it is facilitated when the noise shares common amplitude modulations across a wide frequency range, due to a phenomenon called comodulation masking release (CMR). Here, we examined how properties of the background noise, such as its bandwidth and amplitude modulation, influence the detection threshold of a target sound (pulsed amplitude modulated tones) by single neurons in the frog auditory midbrain. We found that for both modulated and unmodulated masking noise, masking was generally stronger with increasing bandwidth, but it was weakened for the widest bandwidths. Masking was less for modulated noise than for unmodulated noise for all bandwidths. However, responses were heterogeneous, and only for a subpopulation of neurons the detection of the probe was facilitated when the bandwidth of the modulated masker was increased beyond a certain bandwidth - such neurons might contribute to CMR. We observed evidence that suggests that the dips in the noise amplitude are exploited by TS neurons, and observed strong responses to target signals occurring during such dips. However, the interactions between the probe and masker responses were nonlinear, and other mechanisms, e.g., selective suppression of the response to the noise, may also be involved in the masking release.
Journal of Neurophysiology · Feb 2012
Ian Nauhaus, Kristina J. Nielsen, Edward M. Callaway
Abstract
We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates. The observed relationship is consistent with saturation that clips the high-contrast tuning curve peaks by ∼40%. The nonlinearity was also apparent in mouse V1 responses to drifting gratings, but not as strong as in the ferret. Contrast invariance holds, however, for tuning curves measured with a randomized grating stimulus. This finding is consistent with prior work showing that the linear portion of a linear-nonlinear system can be recovered with reverse correlation. Furthermore, we demonstrate that a noise stimulus is more effective at keeping spike rates in the linear operating regime of a saturating nonlinearity, which both maximizes signal-to-noise ratios and simplifies the recovery of fast spike dynamics from slow calcium transients. Finally, we uncover spatiotemporal receptive fields by removing the nonlinearity and slow calcium transient from a model of fluorescence generation, which allowed us to observe dynamic sharpening of orientation tuning. We conclude that for two-photon recordings it is imperative that one considers the nonlinear distortion when designing stimuli and interpreting results, especially in sensory areas, species, or cell types with high firing rates.
Journal of Neurophysiology · Feb 2012
Wei-Li Diana Ma, Stephan D. Brenowitz
Abstract
Because of the availability of disease and genetic models, the mouse has become a valuable species for auditory neuroscience that will facilitate long-term goals of understanding neuronal mechanisms underlying the perception and processing of sounds. The goal of this study was to define the basic sound-evoked response properties of single neurons in the mouse dorsal cochlear nucleus (DCN). Neurons producing complex spikes were distinguished as cartwheel cells (CWCs), and other neurons were classified according to the response map scheme previously developed in DCN. Similar to observations in other rodent species, neurons of the mouse DCN exhibit relatively little sound-driven inhibition. As a result, type III was the most commonly observed response. Our findings are generally consistent with the model of DCN function that has been developed in the cat and the gerbil, suggesting that this in vivo mouse preparation will be a useful tool for future studies of auditory physiology.
Critical Care Medicine · Feb 2012
Anil Maybhate, Charles Hu, Faith A. Bazley, … Angelo H. All
Abstract
Objective: Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury, the primary focus has been assessing the effects of hypothermia on behavioral and histologic outcomes. Although a few studies have investigated electrophysiological changes in descending motor pathways with motor-evoked potentials recorded during cooling, we report here hypothermia induced increased electrical conduction in the ascending spinal cord pathways with somatosensory-evoked potentials in injured rats. In our experiments, these effects lasted long after the acute hypothermia and were accompanied by potential long-term improvements in motor movement. Design: Laboratory investigation. Setting: University medical school. Subjects: Twenty-one female Lewis rats. Interventions: Hypothermia. Measurements and main results: All animals underwent spinal cord contusion with the NYU-Impactor by a 12.5-mm weight drop at thoracic vertebra T8. A group (n = 10) was randomly assigned for a systemic 2-hr hypothermia episode (32 ± 0.5°C) initiated approximately 2.0 hrs postinjury. Eleven rats were controls with postinjury temperature maintained at 37 ± 0.5°C for 2 hrs. The two groups underwent preinjury, weekly postinjury (up to 4 wks) somatosensory-evoked potential recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histologic analysis at postinjury day 3 and day 28. Compared with controls, the hypothermia group showed significantly higher postinjury somatosensory-evoked potential amplitudes with longer latencies. The BBB scores were also higher immediately after injury and 4 wks later in the hypothermia group. Importantly, specific changes in the Basso, Beattie, Bresnahan scores in the hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histologic evaluations showed more tissue preservation in the hypothermia group. Conclusions: After spinal cord injury, early systemic hypothermia provided significant neuroprotection weeks after injury through improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and postacute periods after injury.