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Timothy E Holy

Publications and source records attributed to Timothy E Holy.

6 recordsLinked to original sources

Singing mice, songbirds, and more: models for FOXP2 function and dysfunction in human speech and language.

In 2001, a point mutation in the forkhead box P2 (FOXP2) coding sequence was identified as the basis of an inherited speech and language disorder suffered by members of the family known as "KE." This mini-symposium review focuses on recent findings and research-in-progress, primarily from five laboratories. Each aims at capitalizing on the FOXP2 discovery to build a neurobiological bridge between molecule and phenotype. Below, we describe genetic through behavioral techniques used currently to investigate FoxP2 in birds, rodents, and humans for discovery of the neural bases of vocal learning and language.

Animals↗

Physiologic diversity and development of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate numerous nonvisual phenomena, including entrainment of the circadian clock to light-dark cycles, pupillary light responsiveness, and light-regulated hormone release. We have applied multielectrode array recording to characterize murine ipRGCs. We find that all ipRGC photosensitivity is melanopsin dependent. At least three populations of ipRGCs are present in the postnatal day 8 (P8) murine retina: slow onset, sensitive, fast off (type I); slow onset, insensitive, slow off (type II); and rapid onset, sensitive, very slow off (type III). Recordings from adult rd/rd retinas reveal cells comparable to postnatal types II and III. Recordings from early postnatal retinas demonstrate intrinsic light responses from P0. Early light responses are transient and insensitive but by P6 show increased photosensitivity and persistence. These results demonstrate that ipRGCs are the first light-sensitive cells in the retina and suggest previously unappreciated diversity in this cell population.

Action Potentials↗

Ultrasonic songs of male mice.

Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30-110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure. This study provides a quantitative initial description of male mouse songs, and opens the possibility of studying song production and perception in an established genetic model organism.

Animals↗

Wake up and smell the conspecific!

Mammals regulate their behavior using odor cues called pheromones. These compounds are detected and recognized by neurons in the accessory olfactory system. New electrophysiological recordings in behaving mice by Luo, Fee and Katz reveal aspects of pheromone biology and how these stimuli are represented by single neurons.

Animals↗

Loss of sex discrimination and male-male aggression in mice deficient for TRP2.

The mouse vomeronasal organ (VNO) is thought to mediate social behaviors and neuroendocrine changes elicited by pheromonal cues. The molecular mechanisms underlying the sensory response to pheromones and the behavioral repertoire induced through the VNO are not fully characterized. Using the tools of mouse genetics and multielectrode recording, we demonstrate that the sensory activation of VNO neurons requires TRP2, a putative ion channel of the transient receptor potential family that is expressed exclusively in these neurons. Moreover, we show that male mice deficient in TRP2 expression fail to display male-male aggression, and they initiate sexual and courtship behaviors toward both males and females. Our study suggests that, in the mouse, sensory activation of the VNO is essential for sex discrimination of conspecifics and thus ensures gender-specific behavior.

Aggression↗