Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices.

The cooperation of sustained and phasic inhibitions increases the contrast of ITD-tuning in low-frequency neurons of the chick nucleus laminaris.

Neurons in the nucleus laminaris (NL) of birds detect the coincidence of binaural excitatory inputs from the nucleus magnocellularis (NM) on both sides and process the interaural time differences (ITDs) for sound localization. Sustained inhibition from the superior olivary nucleus is known to control the gain of coincidence detection, which allows the sensitivity of NL neurons to ITD tolerate strong-intensity sound. Here, we found a phasic inhibition in chicken brain slices that follows the ipsilateral NM inputs after a short time delay, sharpens coincidence detection, and may enhance ITD sensitivity in low-frequency NL neurons. GABA-positive small neurons are distributed in and near the NL. These neurons generate IPSCs in NL neurons when photoactivated by a caged glutamate compound, suggesting that these GABAergic neurons are interneurons that mediate phasic inhibition. These IPSCs have fast decay kinetics that is attributable to the α1-subunit of the GABAA receptor, the expression of which dominates in the low-frequency region of the NL. Model simulations demonstrate that phasic IPSCs narrow the time window of coincidence detection and increase the contrast of ITD-tuning during low-level, low-frequency excitatory input. Furthermore, cooperation of the phasic and sustained inhibitions effectively increases the contrast of ITD-tuning over a wide range of excitatory input levels. We propose that the complementary interaction between phasic and sustained inhibitions is the neural mechanism that regulates ITD sensitivity for low-frequency sound in the NL.

Sound-intensity-dependent compensation for the small interaural time difference cue for sound source localization.

Interaural time difference (ITD) is a major cue for sound source localization. However, animals with small heads experience small ITDs, making ITD detection difficult, particularly for low-frequency sound. Here, we describe a sound-intensity-dependent mechanism for compensating for the small ITD cues in the coincidence detector neurons in the nucleus laminaris (NL) of the chicken aged from 3 to 29 d after hatching. The hypothesized compensation mechanisms were confirmed by simulation. In vivo single-unit recordings revealed an improved contrast of ITD tuning in low-best-frequency (<1 kHz) NL neurons by suppressing the firing activity at the worst ITD, whereas the firing rate was increased with increasing sound intensity at the best ITD. In contrast, level-dependent suppression was so weak in the middle- and high-best-frequency (> or =1 kHz) NL neurons that loud sounds led to increases in firing rate at both the best and the worst ITDs. The suppression of firing activity at the worst ITD in the low-best-frequency neurons required the activation of the superior olivary nucleus (SON) and was eliminated by electrolytic lesions of the SON. The frequency-dependent suppression reflected the dense projection from the SON to the low-frequency region of NL. Thus, the small ITD cues available in low-frequency sounds were partly compensated for by a sound-intensity-dependent inhibition from the SON.

The modulation by intensity of the processing of interaural timing cues for localizing sounds.

Features of sounds such as time and intensity are important binaural cues for localizing their sources. Interaural time differences (ITDs) and interaural level differences are extracted and processed in parallel by separate pathways in the brainstem auditory nuclei. ITD cues are small, particularly in small-headed animals, and processing of these cues is optimized by both morphological and physiological specializations. Moreover, recent observations in mammals and in some birds indicate that interaural time and level cues are not processed independently but cooperatively to improve the detection of interaural differences. This review will specifically summarize what is known about how inhibitory circuits improve the measurements of ITD in a sound-level-dependent manner.

Chiari type 1 malformation associated with central sleep apnea after high dose growth hormone (GH) therapy in a 12-year-old boy: A case report.

We describe the case of a short-statured 12-yr-old boy who developed a Chiari type 1 malformation associated with central sleep apnea after administration of high-dose GH therapy, which he had been receiving since the age of 10 yr and 4 mo. He responded well to GH therapy, and his height increased by 18.8 cm in 2 yr. At 12 yr and 4 mo of age, his mother reported that he had developed sleep apnea during the previous year and it had worsened over a month prior to presentation at our hospital. Otolaryngological examination did not reveal tonsillar or adenoidal hypertrophy. Polysomnography demonstrated severe central sleep apnea with an apnea-hypopnea index of 46.5/h. Sagittal T1-weighted magnetic resonance imaging (MRI) demonstrated herniation of the cerebellar tonsils 15 mm below the foramen magnum into the cervical spinal cord. Continuous positive airway pressure therapy initiated prior to performing neurosurgery was ineffective. Following uncomplicated foramen magnum decompression, his breathing pattern during sleep returned to normal. Sagittal MRI examination should be considered in patients who develop sleep apnea during/following administration of GH therapy.