本研究では、聴覚神経系で入力の統合を担う下丘におけるシナプス伝達特性の生後発達段階における変化について、シナプス電流をパッチクランプ法で計測した。NMDA-EPSCにおいて、聴覚入力開始後に減衰時間が短縮していた。上行性経路からのシナプス伝達では、発達段階に応じて短期シナプス可塑性が変化した。一方で、交連性経路からのシナプス伝達では、発達段階に伴う短期シナプス可塑性の傾向には有意な変化はなかった。 / The inferior colliculus (IC) is the primal center of convergence and integration in the auditory pathway. I have measured excitatory synaptic currents (EPSCs) of the neurons in the central nucleus of the IC in response to stimulation of the lateral lemniscus and the commissure of the IC. Before hearing onset, the lemniscus inputs exhibited short-term depression, whereas commissural inputs showed facilitation. After hearing onset, the NMDA-EPSCs exhibited faster decay for both pathways. Furthermore, the EPSCs showed less short-term plasticity in both pathways. These developmental changes may ensure faster and more reliable signal transmission to the IC after onset of hearing. / 博士(理学) / Doctor of Philosophy in Science / 同志社大学 / Doshisha University

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<p>Neurons throughout the auditory pathway respond selectively to the frequency and amplitude of sound. In the auditory midbrain there exists a class of neurons that are also selective to the duration of sound. These duration-tuned neurons (DTNs) provide a potential neural mechanism underlying temporal processing in the central nervous system. Temporal processing is necessary for human speech, discriminating species-specific acoustic signals as well as echolocation. This dissertation aims to explore the role and underlying mechanisms of DTNs through single-unit in vivo electrophysiological recordings in the auditory midbrain of the big brown bat. The durations that DTNs are selective to in echolocating and non-echolocating species are first compared to the durations of each species vocalizations. This comparison reveals that the durations DTNs respond best to correlates to the durations of echolocation calls in echolocating species and to species-specific communication calls in non-echolocating species. The ability of DTNs in the bat to respond to stimulus parameters thought to be important for echolocation processing, such as pairs of pulses and binaural sound localization cues, are subsequently tested. The responses of DTNs to a paired tone spike suppressing paradigm presented monaurally and binaurally are also compared to characterize the role each ear plays in recruiting inhibition known to be involved in duration tuning. The results show that DTNs are able to respond to pairs of pulses at a timescale relevant to bat echolocation, and a majority also responded selectively to binaural sound localizing cues. Nearly half (48%) of DTNs did not show spike suppression to an ipsilaterally presented suppressing tone. When ipsilaterally evoked spike suppression occurred, the effect was significantly smaller than the suppression evoked by a contralateral suppressing tone. These findings provide evidence that DTNs may play a role in echolocation in bats as DTNs are able to respond to the outgoing pulse and returning echoes and localize the echo source and that the neural mechanism underlying duration tuning is monaural in nature.</p> / Doctor of Philosophy (PhD)

Auditory neurons selectively respond to frequency and amplitude of sound. In the auditory midbrain, duration-tuned neurons (DTNs) are subsets of neurons that selectively respond to the duration of sound. DTNs may help further understand the neural mechanism underlying temporal processing in the central nervous system. Temporal processing has been shown to play important roles in speech, discriminating species-specific signals, and echolocation. The goal of this thesis is to explore the role of DTNs through single-unit electrophysiological recordings in the auditory midbrain of the big brown bat (Eptesicus fuscus). Monotic and dichotic paired-tone stimulation was used to evoke excitatory and inhibitory responses from DTNs. Two stimuli consisted of best duration (BD) excitatory and non-excitatory (NE) tones. In the monotic condition, both tones were presented to the contralateral ear, and when they were close in time, the NE tone always suppressed spikes evoked by the BD tone. In the dichotic condition, the BD tone was presented to the contralateral ear. The NE tone was presented to the ipsilateral ear and suppressed BD tone evoked spiking in ~50% of cells. Properties of the ipsilaterally-evoked inhibition were investigated by varying the frequency of the NE tone from the best excitatory frequency (BEF), throughout a cell’s excitatory bandwidth (eBW). We measured the inhibitory frequency response area, best inhibitory frequency (BIF), and inhibitory bandwidth (iBW) of each cell. We found inhibition became weaker as the frequency of the NE tone moved further from the middle of the eBW. We found that a DTN’s BEF and BIF closely matched, but the eBW was broader than the iBW and overlapped the iBW measured from the same cell. This suggests temporal selectivity of midbrain DTNs are created by monaural inputs, with binaural inputs playing a lesser role in shaping duration selectivity. / Thesis / Master of Science (MSc)

Many neurons in the auditory midbrain are tuned to binaural cues. Two prominent binaural cues are the interaural intensity difference (IID) and the interaural time difference (ITD). The ITD cue can further be classified as either an ongoing ITD, which compares the phase difference in the waveform of low frequency stimuli present at either ear, or an onset ITD, which compares the onset time of arrival of two stimuli at either ear. Little research has been done on the sensitivity of single neurons to onset ITDs in the auditory system, particularly in bats. The current study examines the response properties of neurons in the inferior colliculus (IC) of the big brown bat, Eptesicus fuscus, to onset ITDs in response to high frequency pure tones. Measures of neurons’ dynamic response—the segment of the ITD function exhibiting the highest rate of change in activity—revealed an average change of 36% of its maximum response within the estimated behaviorally relevant range of ITDs. Time-intensity trading describes the ability of the brain to compensate the binaural time cue (ITD) cue for the binaural intensity cue (IID) and can be measured as the horizontal shift of an ITD function at various IIDs. Across all IC neurons, an average time-intensity trading ratio of 30 μs/dB was calculated to measure the sensitivity of IC neurons’ ITD response to changing IIDs. Minimum and maximum ITD responses were found to be clustered within a narrow range of ITDs. The average peak ITD response occurred at 268 μs and is consistent with findings in other mammals. All results in ITD tuning, time-intensity trading, and response maximum were invariant to stimulus frequency, confirming that IC neurons responded to onset ITDs and not ongoing ITDs. These results suggest the potential for high frequency onset cues to assist in the azimuthal localization of sound in echolocating bats. / Thesis / Master of Science (MSc)

A Cetamina, antagonista não competitivo de receptores de glutamato do tipo NMDA, é uma substância com propriedades dissociativas originalmente utilizada como anestésico que apresenta a característica de intensificar as experiências sensoriais. Apesar de seus conhecidos efeitos sobre os aspectos cognitivos e comportamentais, poucos estudos préclínicos foram conduzidos para tentar detectar os efeitos físicos e/ou comportamentais da abstinência de Cetamina após consumo prolongado. Partindo do princípio de que os efeitos da Cetamina sobre a neurotransmissão glutamatérgica induzem alguns dos sintomas observados durante surtos esquizofrênicos, como as alucinações auditivas, e sabendo que o colículo inferior tem sua função ligada ao processamento da informação sensorial a estímulos sonoros, neste estudo avaliamos os efeitos da modulação glutamatérgica na área cortical pré-límbica (PrL) sobre os potenciais evocados auditivos eliciados (PEAs) no colículo inferior. As medidas foram realizadas no fim do tratamento, ou seja, no 14° dia, 24 horas e 6 dias após a retirada da cetamina. Em nossos resultados obtivemos que a administração local de NMDA, foi capaz de diminuir a amplitude dos PEAs, os quais foram recuperados 24 horas após. A cetamina sistêmica não foi capaz de diminuir os PEAs, uma provável consequência da interação com outros receptores além do NMDA. Os testes realizados 6 dias após a interrupção ao tratamento crônico de cetamina, demonstraram uma forma inesperada de U, diferente da curva padrão de U invertido. Além disso, encontramos que as alterações provocadas pela cetamina são dependentes dos níveis dos mecanismos dopaminérgico e glutamatérgicos. Estes resultados demonstram que o processamento auditivo no colículo inferior está sob controle direto no Pré límbico e permitem ampliar o conhecimento atual da neurobiologia por evidenciar novas informações do efeito crônico da cetamina. / Ketamine is a non-competitive NMDA receptor antagonist. It is a substance with dissociative properties originally used as anesthetic, which can intensify sensory experiences, being also capable of accentuating the psychotic state in patients with schizophrenia. Despite its known effect on cognitive aspects and behavior, there are few preclinical studies conducted to identify physical and behavioral effects of ketamine withdrawal after its long-term use. Moreover, little is known about the impact of repetitive use of ketamine on brain structures and their functioning. The inferior colliculus, part of the midbrain tectum, is mainly related to auditory information processing, sending information to the motor centers and participating in the modulation and expression of specific behaviors, such as attack and predatory. Therefore, it is related to the biological importance of sounds to survival. The auditory hallucinations induced by schizophrenic psychotic crisis has as neural correspondent the activation of inferior colliculus and cortical areas. It is not yet known which cortical area is connected to the modulation of alterations induced by electrophysiological potential registered in inferior colliculus. Considering that the effects of ketamine on glutamate neurotransmission induces the symptoms observed during schizophrenic psychotic crisis, such as auditory hallucinations, and that inferior colliculus is related to the sensory information processing and auditory pathways, the present work evaluates the effects of glutamate modulation on pre-limbic cortical area on auditory evoked potential startle in inferior colliculus of rats tested during and after interruption of chronic treatment with ketamine

Many cells in the inferior colliculus (IC) are excited by contralateral and inhibited by ipsilateral stimulation and are thought to be important for sound localization. These excitatory-inhibitory (EI) cells comprise a diverse group, even though they exhibit a common binaural response property. Previous extracellular studies proposed specific excitatory and/or inhibitory events that should be evoked by each ear and thereby generate each of the EI discharge properties. The proposals were inferences based on the well established response features of neurons in lower nuclei, the projections of those nuclei, their excitatory or inhibitory neurochemistry, and the changes in response features that occurred when inhibition was blocked. Here we recorded the inputs, the postsynaptic potentials, discharges evoked by monaural and binaural signals in EI cells with in vivo whole cell recordings from the inferior colliculus (IC) of awake bats. We also computed the excitatory and inhibitory synaptic conductances from the recorded sound evoked responses. First, we showed that a minority of EI cells either inherited their binaural property from a lower binaural nucleus or the EI property was created in the IC via inhibitory projections from the ipsilateral ear, features consistent with those observed in extracellular studies. Second, we showed that in a majority of EI cells ipsilateral signals evoked subthreshold EPSPs that behaved paradoxically in that EPSP amplitudes increased with intensity, even though binaural signals with the same ipsilateral intensities generated progressively greater spike suppressions. These ipsilateral EPSPs were unexpected since they could not have been detected with extracellular recordings. These additional responses suggested that the circuitry underlying EI cells was more complex than previously suggested. We also proposed the functional significance of ipsilaterally evoked EPSPs in responding to moving sound sources or multiple sounds. Third, by computing synaptic conductances, we showed the circuitry of the EI cells was even more complicated than those suggested by PSPs, and we also evaluated how the binaural property was produced by the contralateral and ipsilateral synaptic events. / text

Natural sound, such as conspecific vocalizations and human speech, represents an important part of the sensory signals animals and humans encounter in their daily lives. This dissertation investigates the neural mechanisms involved in creating response selectivity for complex features of natural acoustic signals and demonstrates that selectivity for spectral motion cues provides a neural mechanism to encode communication signals in the auditory midbrain. Spectral motion is defined as the movement of sound energy upward or downward in frequency at a certain velocity, and is believed to provide the auditory system with an important perceptual cue in the processing of human speech. Using the Mexican free-tailed bat, tadarida brasiliensis, as a model system, this research examined the role of selectivity for spectral motion cues, such as direction and velocity, in creating response selectivity for specific features of the social communication signals emitted by these animals. We show that auditory neurons in the midbrain nucleus of the inferior colliculus (IC) are specifically tuned for the frequency-modulated (FM) direction and velocities found in their conspecific vocalizations. This close agreement between neural tuning and features of natural conspecific signals shows that auditory neurons have evolved to specifically encode features of signals that are vital for the survival of the animal. Furthermore, we find that the neural computations resulting in selectivity for spectral motion are analogous to mechanisms observed in selectivity for visual motion, suggesting the evolution of similar neural mechanisms across sensory modalities. / text