Impaired Development and Competitive Refinement of the Cortical Frequency Map in Tumor Necrosis Factor- -Deficient Mice

Abstract

Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development.

Astrocyte function from information processing to cognition and cognitive impairment

“…Through these effects, TNFα contributes to synaptic scaling, a form of homeostatic plasticity by which a population of synapses collectively adjusts its strength to long-term variations in network activity, e.g. during plastic rearrangement of sensory circuits 58,59 . TNFα also affects synaptic strength through regulation of astrocyte glutamate release ( Fig.…”

Auditory map plasticity: diversity in causes and consequences

“…A recent study of the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in mouse primary auditory cortex used the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity [137]. These mice develop weaker tonal responses and incomplete frequency representations.…”

“…For instance, within minutes following exposure to intense noise, spectral and temporal organization of sound-evoked inhibitory synaptic inputs are dysregulated, producing poorly selective ‘noisy’ receptive field organization [145]. Over the course of several weeks, AI neurons become re-tuned to sound frequencies bordering the cochlear lesion [64, 131] in a manner that may depend on homeostatic plasticity mechanisms [137] rather than associative plasticity mechanisms such as modulation from nucleus basalis [146]. (e) Additional work will be needed to unveil the specific homeostatic mechanisms that enable receptive field renormalization following auditory deafferentation.…”

Experience-dependent overrepresentation of ultrasonic vocalization frequencies in the rat primary auditory cortex

“…Receptive fields were isolated using an automated filtering and thresholding algorithm as previously described (Insanally et al 2010;Köver et al 2013;Yang et al 2013). Briefly, receptive fields were smoothed with a 3 ϫ 3 median filter and thresholded at 20% of the maximum response.…”

“…Linear regression analysis of neurons with receptive fields completely contained within 1 and 74 kHz shows a highly significant negative correlation between CF and BW for all six animals (r ϭ Ϫ0.77, P Ͻ 0.0001), showing narrower tuning BW for neurons in the UVF range. Interestingly, experience in multifrequency enriched environments can result in narrower frequency tuning (Köver et al 2013;Yang et al 2013).…”