Browsing by Subject "Sound localization"

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Binaural mechanism revealed with in vivo whole cell patch clamp recordings in the inferior colliculus
(2010-12) Li, Na, 1980 Oct. 2-; Pollak, G. D. (George D.), 1942-; Huk, Alex; Priebe, Nicholas; Golding, Nace; Zakon, Harold; Morrisett, Richard
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.
The interrogation of auditory activity and molecular genetics on the development of sound localization neurons
(2021-08-12) Haimes, David Birkett; Golding, Nace L.; Brager, Darrin; Zakon, Harold; Aldrich, Richard
The body of work presented here is a series of manuscripts in varying states of publication that represent the work performed by the author. In brief, these works have focused on unraveling on a cellular level how the auditory brain builds a spatial map of one’s environment discretely from sound stimuli which fundamentally lack spatial information. Neurons in the brain region known as the Medial Superior Olive (MSO) integrate differences in the arrival time of sound stimuli between two ears, while neurons in the Lateral Superior Olive (LSO) integrate differences in the intensity of sound stimuli. Cells in both regions use their unique strategies to compute spatial information, split based on the frequency of incoming sound. In the manuscripts presented here (Chapter 4), we demonstrate that neurons in the LSO do not strictly adhere to previous historical dogma (use of predominantly high frequency sounds), and instead show exquisite temporal resolution more like MSO neurons. Specifically, our work demonstrates a neural “vetoing” mechanism in which spatially precise inhibition overrides the integration of somatodendritic excitatory signals due to its localization on the axon initial segment of neurons. For the remaining work (Chapters 3 & 5), we discuss how MSO neurons exhibit a continuum of response properties, ranging from neurons with exquisite temporal precision, to neurons with incredibly slow properties that are poor coincidence detectors. These slow MSO neurons were previously assumed to be non-principal neurons, but throughout this body of work we demonstrate that all MSO neurons are principal neurons that exist along a continuum of firing response properties and all project to downstream auditory centers. Furthermore, we deeply investigate how this continuum of response properties arises: whether through development, auditory activity, or an interdependence. Interestingly, the diversity of MSO response properties arises predominantly through developmental changes to the transcriptome of cells. The spectrum of response properties is almost entirely filled out, and only minorly fine-tuned by auditory activity. Together, this data heavily implies that MSO neurons are fated to become coincidence detectors, but across a much wider range of temporal disparities than previously appreciated.