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EphA signaling impacts development of topographic connectivity in auditory corticofugal systems.

ABSTRACT: Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of EphA receptor signaling in the development of corticothalamic (CT) and corticocollicular connections. Early in postnatal development, CT axons were restricted to a deep dorsal zone (DDZ) within the MGB that expressed low levels of the ephrin-A ligand. By hearing onset, CT axons had innervated surrounding regions of MGB in control-electroporated mice but remained fixed within the DDZ in mice overexpressing EphA7. In vivo neurophysiological recordings demonstrated a corresponding reduction in spontaneous firing rate, but no changes in sound-evoked responsiveness within MGB regions deprived of CT innervation. Structural and functional CT disruption occurred without gross alterations in thalamocortical connectivity. These data demonstrate a potential role for EphA/ephrin-A signaling in the initial guidance of corticofugal axons and suggest that "genetic rewiring" may represent a useful functional tool to alter cortical feedback without silencing Actx.

SUBMITTER: Torii M

PROVIDER: S-EPMC3593572 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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EphA signaling impacts development of topographic connectivity in auditory corticofugal systems.

Torii Masaaki M Hackett Troy A TA Rakic Pasko P Levitt Pat P Polley Daniel B DB

Cerebral cortex (New York, N.Y. : 1991) 20120405 4

Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of Eph ...[more]

PMID: 22490549

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Project description:OBJECTIVE:Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Here, we sought to determine whether different modes of corticocollicular activation could titrate the strength of feedforward modulation of sound processing in IC neurons. APPROACH:We used multi-channel electrophysiology and optogenetics to record from multiple regions of the IC in awake head-fixed mice while optogenetically stimulating ACtx neurons expressing Chronos, an ultra-fast channelrhodopsin. To identify cortical activation patterns associated with the strongest effects on IC firing rates, we employed a closed-loop evolutionary optimization procedure that tailored the voltage command signal sent to the laser based on spike feedback from single IC neurons. MAIN RESULTS:Within minutes, our evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that either suppressed or enhanced sound-evoked IC firing rate. SIGNIFICANCE:This study introduces a closed-loop optimization procedure to probe functional connections between brain areas. Our findings demonstrate that the influence of descending feedback projections on subcortical sensory processing can vary both in sign and degree depending on how cortical neurons are activated in time.

Dataset Information

EphA signaling impacts development of topographic connectivity in auditory corticofugal systems.

Publications

EphA signaling impacts development of topographic connectivity in auditory corticofugal systems.

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