Alexander V. Galazyuk

Intracellular Recordings From Combination-Sensitive Neurons in the Inferior Colliculus

In vertebrate auditory systems, specialized combination-sensitive neurons analyze complex vocal signals by integrating information across multiple frequency bands. We studied combination-sensitive interactions in neurons of the inferior colliculus (IC) of awake mustached bats, using intracellular somatic recording with sharp electrodes. Facilitated combinatorial neurons are coincidence detectors, showing maximum facilitation when excitation from low- and high-frequency stimuli coincide. Previous work showed that facilitatory interactions originate in the IC, require both low and high frequency-tuned glycinergic inputs, and are independent of glutamatergic inputs. These results suggest that glycinergic inputs evoke facilitation through either postinhibitory rebound or direct depolarizing mechanisms. However, in 35 of 36 facilitated neurons, we observed no evidence of low frequency-evoked transient hyperpolarization or depolarization that was closely related to response facilitation. Furthermore, we observed no evidence of shunting inhibition that might conceal inhibitory inputs. Since these facilitatory interactions originate in IC neurons, the results suggest that inputs underlying facilitation are electrically segregated from the soma. We also recorded inhibitory combinatorial interactions, in which low frequency sounds suppress responses to higher frequency signals. In 43% of 118 neurons, we observed low frequency-evoked hyperpolarizations associated with combinatorial inhibition. For these neurons, we conclude that low frequency-tuned inhibitory inputs terminate on neurons primarily excited by high-frequency signals; these inhibitory inputs may create or enhance inhibitory combinatorial interactions. In the remainder of inhibited combinatorial neurons (57%), we observed no evidence of low frequency-evoked hyperpolarizations, consistent with observations that inhibitory combinatorial responses may originate in lateral lemniscal nuclei.

Tinnitus and underlying brain mechanisms.

Purpose of reviewTinnitus is the sensation of hearing a sound when no external auditory stimulus is present. Most individuals experience tinnitus for brief, unobtrusive periods. However, chronic sensation of tinnitus affects approximately 17% (44 million people) of the general US population. Tinnitus, usually a benign symptom, can be constant, loud and annoying to the point that it causes significant emotional distress, poor sleep, less efficient activities of daily living, anxiety, depression and suicidal ideation/attempts. Tinnitus remains a major challenge to physicians because its pathophysiology is poorly understood and there are few management options to offer to patients. The purpose of this article is to describe the current understanding of central neural mechanisms in tinnitus and to summarize recent developments in clinical approaches to tinnitus patients. Recent findingsRecently developed animal models of tinnitus provide the possibility to determine neuronal mechanisms of tinnitus generation and to test the effects of various treatments. The latest research using animal models has identified a number of abnormal changes, in both auditory and nonauditory brain regions, that underlie tinnitus. Furthermore this research sheds light on cellular mechanisms that are responsible for development of these abnormal changes. SummaryTinnitus remains a challenging disorder for patients, physicians, audiologists and scientists studying tinnitus-related brain changes. This article reviews recent findings of brain changes in animal models associated with tinnitus and a brief review of clinical approach to tinnitus patients.

Stimulation rate influences frequency tuning characteristics of inferior colliculus neurons in the little brown bat, Myotis lucifugus.

Previous studies of frequency selectivity have investigated units responses to tonal stimuli widely separated in time to minimize inter-stimulus interaction. The results of such studies are assumed to accurately portray the cells frequency selectivity. The goal of the present study was to investigate the frequency tuning characteristics of neurons in the inferior colliculus (IC) of the little brown bat (Myotis lucifugus) to tone pulses presented at higher rates. Our results indicate that the frequency response properties of central auditory neurons at low stimulation rates do not necessarily reflect the units’ frequency response properties to sounds presented at higher, more behaviorally relevant rates. Specifically, IC neurons often show greater frequency selectivity at higher stimulation rates, which presumably confers a greater perceptual frequency resolution.

Sound-triggered suppression of neuronal firing in the auditory cortex: Implications to the residual inhibition of tinnitus

Tinnitus can be suppressed briefly following the offset of an external sound. This phenomenon, termed “residual inhibition,” has been known for almost four decades, although its underlying cellular mechanism remains unknown. In our previous work, we have shown that the majority of neurons in the inferior colliculus (IC) exhibit long lasting suppression of spontaneous activity following the offset of an external sound. The time course of suppression corresponded to the time course of residual inhibition in tinnitus patients. If the suppression is an underlying mechanism, the auditory cortex (AC) neurons should also exhibit suppression because residual inhibition of tinnitus is a perceptual phenomenon. To test this hypothesis, we studied sound evoked suppression in AC neurons of awake CBA/CaJ mice using extracellular recording. Pure tones at neurons’ characteristic frequency and/or wideband noise stimuli 30 s duration were delivered in the free-field. We found that AC neurons exhibited sound-triggered suppr...

FM signals produce a robust paradoxical latency shift that is important for coding of target range in the bat inferior colliculus

Echolocating bats utilize the time delay between an outgoing ultrasonic pulse and its echo to determine target range. Many neurons at the inferior colliculus (IC) and above are tuned to time delays between these sound pulses of unequal amplitudes. Sullivan previously proposed that paradoxical latency shift (PLS), characterized by a quantal increase in firing latency to loud sounds, is important for this attribute because PLS permits coincidence detection that is important for the creation of delay‐tuned responses. In the IC of little brown bats, Galazyuk and Feng recently reported that, in response to tone pulses, the proportion of neurons showing PLS was low (<20%). This study was undertaken to determine whether PLS is a function of the acoustic stimulus. For this, the temporal discharge patterns of single IC neurons were investigated over a broad range of sound levels, using tone pulses at CF as well as FM sound pulses that mimicked bats’ ultrasonic cry as stimuli. For many IC neurons, tone pulses did n...

Stimulation rate influences frequency tuning characteristics of inferior colliculus neurons

Sounds in real world environments such as animal calls and human speech are complex and often occur in rapid succession. In light of this, it is important to gain an understanding of how the rate of acoustic stimulation influences the units’ basic response properties. Previous studies of frequency tuning were generally based on investigating neuronal responses to tonal stimuli presented in isolation, and the results derived therefrom were assumed to accurately portray the cell’s response range. However, the firing history of an auditory neuron has been shown to shape its response to subsequent sounds. The goal of the present study was to investigate the frequency tuning characteristics of neurons in the inferior colliculus (IC) of the little brown bat to tone pulses presented at various rates. Eighty‐five percent of the IC neurons studied showed rate‐dependent changes in their frequency selectivity. Half of these neurons exhibited narrowing of their frequency response range at higher rates. These results ...

Roles of neural oscillation in time domain processing in the bat inferior colliculus

Central auditory neurons in echolocating bats exhibit pulse‐echo delay‐tuned responses. Sullivan (1982) proposed that paradoxical latency shift (PLS), characterized by an increase in response latency to loud sounds, is important for this attribute. At present, the mechanism underlying PLS is unclear. The goal of the present study was to identify the mechanism underlying PLS. The responses of 92 neurons in the inferior colliculus of little brown bats to brief tone pulses at the unit’s CF over a wide range of sound levels were studied. Of these, 16 neurons displayed unit‐specific periodic oscillatory discharges at high sound levels with a characteristic period of 1.3–6.7 ms. The 27 neurons exhibited unit‐specific PLS, with quantal latency shift of 1.2–8.2 ms. In 14 neurons showing PLS, unit’s responses before, during and after iontophoretic application of bicuculline were investigated. Application of bicuculline abolished the PLS and transformed it into periodic discharges, suggesting that neural oscillatio...