The gut microbiota of environmentally enriched mice regulates visual cortical plasticity.

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function, and plasticity. The poorly known "EE-derived signals'' mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis reveals striking differences in intestinal bacteria composition between EE and standard rearing (ST) mice, as well as enhanced levels of short-chain fatty acids (SCFA) in EE mice. Depleting the microbiota of EE mice with antibiotics strongly decreases SCFA and prevents activation of adult ocular dominance plasticity, spine dynamics, and microglia rearrangement. SCFA treatment in ST mice mimics EE induction of ocular dominance plasticity and microglial remodeling. Remarkably, transferring the microbiota of EE mice to ST recipients activates adult ocular dominance plasticity. Thus, experience-dependent changes in gut microbiota regulate brain plasticity.

Bilateral electroretinographic changes induced by unilateral intra-visual cortex inoculation of herpes simplex virus type 1 in BALB/c mice.

Intra-visual cortex inoculation of 10(2) plaque-forming units of herpes simplex virus type 1 (KOS-63) induced physiologic and morphologic retinal changes in 62.3% (33/53) of infected animals; of these, 91% were bilateral. In contrast, inoculation of the same viral titers into the frontal lobe induced retinal alterations in only 13.3% (2/15). Initially, there was a decrease of the b-wave amplitude and retinal sensitivity and necrotic changes of the ganglion cells and nuclei in the inner nuclear layer. Immunoperoxidase staining for virus-specific antigens showed positive staining of the same cell type. Over time, there was a progressive decrease in the electroretinogram until it was extinguished and the retina was replaced by gliotic tissue. Parallel viral recovery studies demonstrated detectable infectious virus in one of eight eyes on day 2 after inoculation and in three of eight eyes on day 4. Thereafter, there was an increase in the percentage of eyes with infectious virus and a concomitant increase in viral titers. Immunoperoxidase staining of brain sections obtained on days 6 through 8 demonstrated virus-specific antigens on cells in the lateral geniculate nuclei and the suprachiasmatic nuclei bilaterally.

Targeting of scrapie lesions and spread of agent via the retino-tectal projection.

Scrapie infectivity and degenerative vacuolation was initially localized within the contralateral superior colliculus following intraocular injection. The time course of these events was prolonged. With the ME7 strain of scrapie in Sincs7 genotype mice, infectivity began to rise in the superior colliculus from about 70 days, followed by the earliest asymmetrical lesions there from 120 days, with death occurring at about 250 days, at which time vacuolar degeneration was widespread in the brain. With other mouse Sinc genotype mouse/agent strain combinations the process was even further prolonged. With 87V scrapie strain in Sincp7 genotype mice the first lesions to appear were in the contralateral tectum at 300 days. It is concluded that scrapie agent can spread within ganglion cell axons.