Furukawa, Shigeto and John C. Middlebrooks. Cortical representation of auditory space: information-bearing features of spike patterns. J Neurophysiol 87: 1749 -1762, 2002; 10.1152/jn.00491.2001. Previous studies have demonstrated that the spike patterns of cortical neurons vary systematically as a function of sound-source location such that the response of a single neuron can signal the location of a sound source throughout 360°of azimuth. The present study examined specific features of spike patterns that might transmit information related to sound-source location. Analysis was based on responses of well-isolated single units recorded from cortical area A2 in ␣-chloralose-anesthetized cats. Stimuli were 80-ms noise bursts presented from loudspeakers in the horizontal plane; source azimuths ranged through 360°in 20°steps. Spike patterns were averaged across samples of eight trials. A competitive artificial neural network (ANN) identified sound-source locations by recognizing spike patterns; the ANN was trained using the learning vector quantization learning rule. The information about stimulus location that was transmitted by spike patterns was computed from joint stimulus-response probability matrices. Spike patterns were manipulated in various ways to isolate particular features. Full-spike patterns, which contained all spike-count information and spike timing with 100-s precision, transmitted the most stimulus-related information. Transmitted information was sensitive to disruption of spike timing on a scale of more than ϳ4 ms and was reduced by an average of ϳ35% when spike-timing information was obliterated entirely. In a condition in which all but the first spike in each pattern were eliminated, transmitted information decreased by an average of only ϳ11%. In many cases, that condition showed essentially no loss of transmitted information. Three unidimensional features were extracted from spike patterns. Of those features, spike latency transmitted ϳ60% more information than that transmitted either by spike count or by a measure of latency dispersion. Information transmission by spike patterns recorded on single trials was substantially reduced compared with the information transmitted by averages of eight trials. In a comparison of averaged and nonaveraged responses, however, the information transmitted by latencies was reduced by only ϳ29%, whereas information transmitted by spike counts was reduced by 79%. Spike counts clearly are sensitive to sound-source location and could transmit information about sound-source locations. Nevertheless, the present results demonstrate that the timing of the first poststimulus spike carries a substantial amount, probably the majority, of the location-related information present in spike patterns. The results indicate that any complete model of the cortical representation of auditory space must incorporate the temporal characteristics of neuronal response patterns. I N T R O D U C T I O NThe spike patterns of auditory cortical neurons vary systematically as a function o...

A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR) that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants' pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention.

Aberrant activation of Wnt signalling results in colorectal tumours. Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. Lgr5-positive stem cells are responsible for the intestinal adenoma initiated by mutations in adenomatous polyposis coli. Furthermore, Lgr5 interacts with R-spondins and thereby activates Wnt signalling. However, the function of Lgr5 in colorectal tumourigenesis is unclear. Here we show that LGR5 is required for the tumourigenicity of colorectal cancer cells. We show that the transcription factor GATA6 directly enhances the expression of LGR5. We further demonstrate that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. Moreover, we show that overexpression of miR-363 suppresses the tumourigenicity of colorectal cancer cells. These results suggest that the miR-363-GATA6-LGR5 pathway is critical for colorectal tumourigenesis and would be a promising target for the treatment of colorectal cancer.

The present study measured the head-related transfer functions (HRTFs) of the Mongolian gerbil for various sound-source directions, and explored acoustical cues for sound localization that could be available to the animals. The HRTF exhibited spectral notches for frequencies above 25 kHz. The notch frequency varied systematically with source direction, and thereby characterized the source directions well. The frequency dependence of the acoustical axis, the direction for which the HRTF amplitude was maximal, was relatively irregular and inconsistent between ears and animals. The frequency-by-frequency plot of the interaural level difference (ILD) exhibited positive and negative peaks, with maximum values of 30 dB at around 30 kHz. The ILD peak frequency had a relatively irregular spatial distribution, implying a poor sound localization cue. The binaural acoustical axis (the direction with the maximum ILD magnitude) showed relatively orderly clustering around certain frequencies, the pattern being fairly consistent among animals. The interaural time differences (ITDs) were also measured and fell in a +/- 120 micros range. When two different animal postures were compared (i.e., the animal was standing on its hind legs and prone), small but consistent differences were found for the lower rear directions on the HRTF amplitudes, the ILDs, and the ITDs.

We examined the coding of sound-source location by ensembles of neurons in the auditory cortex. Broadband noise bursts were presented from loudspeakers throughout 360 degrees in the horizontal plane. Sound levels varied from 20 to 40 dB above neural thresholds. We recorded temporal spike patterns simultaneously at 16 recording sites in area A2 of alpha-chloralose-anesthetized cats. Spike patterns of individual units varied in spike counts and in spike timing as a function of sound-source location. Ensembles of up to 19 units recorded simultaneously demonstrated additional location sensitivity in the form of relative spike counts and relative spike timing among neurons. We used an artificial neural network (ANN) algorithm to recognize ensemble spike patterns and, thereby, to infer the locations of sound sources. The ANN could estimate stimulus locations based on ensemble responses to single-stimulus presentations. Median errors (MEs) averaged 49.2 +/- 11.9 degrees (mean +/- SD; n = 34; chance level, 90 degrees ). The ANN maintained better-than-chance performance even when input spike patterns were expressed as relative spike counts across units (i.e., no information available from absolute spike counts of individual units; ME, 63.0 +/- 11.8 degrees ) or when spike latencies were represented as time relative to the first spike for each trial (i.e., no external time reference available; ME, 54.3 +/- 12.4 degrees ). The ANN performance improved monotonically as the sizes of ensemble patterns were increased by combining patterns across the entire unit sample. The performance by ensembles of 128 units approached the level of localization performance of behaving cats.