Yutaka Hosokawa

Optical imaging of spatiotemporal patterns of glutamatergic excitation and GABAergic inhibition in the guinea-pig auditory cortex in vivo.

1. Glutamatergic excitation and gamma‐aminobutyric acid (GABA)‐ergic inhibition in layers II and III of the auditory cortex of anaesthetized guinea‐pigs were recorded optically using a voltage‐sensitive dye RH795 and a 12 x 12 photodiode array. 2. After contralateral ear stimulation with pure tones, transient excitatory responses followed by inhibitory responses were observed in fields A (primary) and DC of the auditory cortex. The area of the excitatory responses was sandwiched or surrounded by the areas of the inhibitory responses. 3. Optically recorded excitatory responses to pure tones had two components: a component sensitive to 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), a non‐N‐methyl‐D‐aspartate (non‐NMDA) receptor antagonist, and a component sensitive to 2‐amino‐5‐phosphono‐valerate (APV), an NMDA receptor antagonist. Application of CNQX (5 microM) to the auditory cortex suppressed an early, but not a late, phase of the excitation; application of APV (100 microM) had the opposite effect. Concomitant application of CNQX and bicuculline methiodide (BMI, 4 microM), a GABAA receptor antagonist, increased the amplitude of the late phase 4‐fold. This enhanced response was suppressed by APV. 4. These results indicate that (i) auditory cortical excitatory responses are mediated by both non‐NMDA and NMDA receptors, (ii) inhibition is mediated by GABAA receptors, (ii) the excitatory bands are sandwiched or surrounded by GABAA receptor‐mediated inhibitory areas and (iv) GABAA receptors effectively inhibit the NMDA, but not the non‐NMDA, receptor‐mediated excitation.

Optical imaging of neural activity in multiple auditory cortical fields of guinea pigs

Neural activity of multiple fields in the auditory cortex of anesthetized guinea pigs in response to pure tones was visualized by optical recording using a voltage-sensitive dye (RH795). Ten auditory fields were identified based on the tonotopic organization and response latency: the core fields consisting of the primary (AI) and secondary (AII) fields and surrounding belt areas consisting of dorso-anterior (DA), dorsal (D), dorso-posterior (DP), posterior (P), ventro-poster- ior (VP), ventro-medial (VM), ventro-anterior (VA) and ventral (V) fields. Tonotopic organization was observed in all the fields apart from DA, D, DP and V. Spatio-temporal displays suggest that the auditory information spreads from the core fields of AI and AII to belt fields via three distinct (dorsocaudal, caudal and ventrorostral) pathways.

Alternating current induced otoacoustic emissions in the guinea pig

Injection of alternating current (AC) into the scala media of the guinea pig cochlea induced otoacoustic emissions (OAEs) at the frequency of the AC fundamental, together with harmonic and intermodulation distortion products. Although the waveform of the injected ACs was distorted, probably due to nonlinear polarization of the metal electrodes, and was composed of the fundamental plus distortion products of every order, only a few of the lowest order distortion products were selectively emitted with the fundamental. AC injection at a basal site extended the high frequency limit of OAEs. Electrical stimulation of the crossed olivocochlear bundle inhibited the sideband emissions with little change in the fundamental. OAE was reduced reversibly by temporary impairment of the cochlea due to exposure to fatiguing sound, by intravenous application of furosemide and by temporary anoxia. Irreversible reduction resulted from intracochlear perfusion with excess K+ solution, acoustic trauma and cardiac arrest. These facts imply that AC-induced OAE is not an artifact generated electrically; rather, such emissions originate in the cochlea and normal metabolic activity in the cochlea is essential. A proposed mechanism of generation includes two components: 1) electromechanical transduction from AC to mechanical vibration in the cochlea and 2) a distortion-producing process; the contribution of each component to the receptor mechanism is discussed.

Optical Imaging of Neural Activity in Auditory Cortex Induced by Intracochlear Electrical Stimulation

Little is known about the representation of electrically evoked activity in the auditory cortex. We observed evoked activity in guinea pig auditory cortex evoked by acoustical and electrical stimulation to the cochlea by optical imaging with the aid of a voltage-sensitive dye. Light signals from the cortex were recorded with a 12 x 12 array of photodiodes, and transferred to the spatio-temporal images by every 0.57 ms. The activity by pure tones was shown spatio-temporally through tonotopical organization in the cortex according to the sound frequencies. The tonotopic responses were dynamically changed. When the cochlea was stimulated with single electrical pulses, focal activities were observed in the cortex as spatio-temporal patterns. Activated cortical regions were not sharply localized, but varied with stimulating positions of the cochlea. The curves of response magnitude versus stimulus intensity showed the narrow dynamic range, and that of latency was almost constant. These results were significantly different from those for normal sound stimulation.

Optical study of spatiotemporal inhibition evoked by two-tone sequences in the guinea pig auditory cortex

Abstract Spatiotemporal response patterns in the anterior and dorsocaudal fields of the guinea pig auditory cortex after two-tone sequences were studied in anesthetized animals (Nembutal 30 mg kg−1) using an optical recording method (voltage-sensitive dye RH795, 12 × 12 photodiode array). Each first (masker) and second (probe) tone was 30 ms long with a 10-ms rise-fall time. Masker-probe pair combinations of the same or different frequencies with probe delays of 30–150 ms were presented to the ear contralateral to the recording side. With same-frequency pairs, responses to the probe were inhibited completely after probe delays of less than 50 ms and the inhibition lasted for more than 150 ms, and the inhibition magnitudes in different isofrequency bands of the anterior field were essentially the same. With different-frequency (octave-separated) pairs, responses to the probe were not inhibited completely even after probe delays as short as 30 ms, and the inhibition lasted only for 110–130 ms. Inhibition magnitudes were different from location to location.

Spatiotemporal dynamics of neural activity related to auditory induction in the core and belt fields of guinea-pig auditory cortex.

Auditory induction is a continuity illusion in which missing sounds are perceived under appropriate conditions, for example, when noise is inserted during silent gaps in the sound. To elucidate the neural mechanisms underlying auditory induction, neural responses to tones interrupted by a silent gap or noise were examined in the core and belt fields of the auditory cortex using real-time optical imaging with a voltage-sensitive dye. Tone stimuli interrupted by a silent gap elicited responses to the second tone following the gap as well as early phasic responses to the first tone. Tone stimuli interrupted by broad-band noise (BN), considered to cause auditory induction, considerably reduced or eliminated responses to the tone following the noise. This reduction was stronger in the dorsocaudal field (field DC) and belt fields compared with the anterior field (the primary auditory cortex of guinea pig). Tone stimuli interrupted by notched (band-stopped) noise centered at the tone frequency, considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. These results suggest that substantial changes between responses to silent gap-inserted tones and those to BN-inserted tones emerged in field DC and belt fields. Moreover, the findings indicate that field DC is the first area in which these changes emerge, suggesting that it may be an important region for auditory induction of simple sounds.

Optical imaging of binaural interaction in multiple fields of the guinea pig auditory cortex.

Locating the source of a sound is an important function of the auditory system and interaural intensity differences are one of the most important cues. To study the functional pathways of sound localisation processing in the auditory cortex, activity in multiple fields of the guinea pig auditory cortex during stimulation with interaural intensity differences was studied using optical imaging with a voltage-sensitive dye. Of the auditory core (primary and dorsocaudal) and the belt fields which surround them, the posterior and ventroposterior belt fields were the most sensitive to interaural intensity differences. This suggests that the caudal pathway of the auditory cortex is involved in sound localisation.

REAL-TIME IMAGING OF NEURAL ACTIVITY DURING BINAURAL INTERACTION IN THE GUINEA PIG AUDITORY CORTEX

Abstract Spatio-temporal patterns of binaural interaction in the guinea pig auditory cortex (AC) were observed using optical recording with a 12 × 12 photodiode array and a voltage-sensitive dye. The amplitudes of the sound-induced light signals from the cortex were transformed into sequential two-dimensional images every 0.58 ms. Binaural sound stimuli evoked an excitatory response followed by a strong inhibition, and contralateral stimuli evoked a strong excitatory response followed by a weak inhibition. Ipsilateral sound stimuli evoked a weak response. Binaural stimulation induced two types of ipsilateral inhibition: a fast binaural inhibition which was detected only after the contralateral and ipsilateral responses were subtracted from the binaural responses, and which appeared 12–25 ms after the onset of stimulation, and a slow binaural inhibitory effect which was clearly observed in the binaural responses themselves, appearing 70–95 ms after the onset of stimulation. The fast binaural inhibition was observed in the same area as the contralateral excitatory response. The inhibited area became stronger and more widespread with increasing intensity of ipsilateral stimulation. We did not observe the specialized organization of binaural neurons as electrophysiologically found in the cat AC, in which binaural neurons of the same binaural response type are clustered together and alternate with clusters of other response types.

Spatiotemporal representation of binaural difference in time and intensity of sound in the guinea pig auditory cortex.

Neural activity of the auditory cortex (AC) in response to a change of interaural intensity difference (IID) and interaural time difference (ITD) of sound stimuli was observed by optical recording with a 12 x 12 photodiode array and the voltage-sensitive dye, RH795. Guinea pigs (280-450 g) were anesthetized with sodium pentobarbital (30 mg/kg) and supplemental doses of neuroleptic solutions. When both ears were stimulated dichotically by tone bursts (14 kHz, 75 dB SPL), excitatory optical signals appeared in both anterior (A) and dorsocaudal (DC) fields of AC. An increase of intensity of ipsilateral stimulation from 65 to 95 dB SPL caused a decrease of neural activity of isofrequency bands in both fields. An increase of ipsilateral leads from -2.5 to 10 ms resulted in a gradual decrease of the amplitude of the excitatory responses. A strong inhibition was observed in field DC and the ventral portion of field A. These results show the different spatiotemporal representation of IID and ITD sensitivities in AC. However, the ipsilateral lead inducing a large inhibition was much longer than the time difference (80 micros) calculated from the interaural distance of the guinea pig. This indicates that the longer binaural inhibition observed in AC would have a different functional significance from that of the neural system of ITD detection in the guinea pig.

Anisotropic neural interaction in the primary auditory cortex of guinea pigs with sound stimulation

NEURAL interaction in the primary auditory cortex of guinea pigs anesthetized with sodium pentobarbital was studied using a single line multi-electrode (4 × 1) aligned across and along the isofrequency band. Under the spontaneous condition, the neural interaction was isotropic; the amplitude of cross-correlogram peaks decreased as the electrode separation increased both across and along the isofrequency band. Under tone stimulation, the neural interaction was anisotropic; the amplitude of peaks was decreased rapidly beyond 400 μm across the isofrequency band, while it decreased little up to 700 μm along the isofrequency band. This anisotropic interaction was dependent on the stimulus intensity.