Chronic Sensory Deprivation Research Articles

Development and sensory experience dependent regulation of microglia in barrel cortex.

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals' first postnatal month. Using immunohistochemistry to label microglia, we performed morphological reconstructions as well as densitometry analyses as a function of developmental age and sensory experience. Findings suggest that both developmental age and sensory experience has profound impact on microglia morphology. Following chronic sensory deprivation, microglia undergo a morphological transition from a monitoring or resting state to an altered morphological state, by exhibiting expanded cell body size and retracted processes. Sensory restoration via whisker regrowth returns these morphological alterations back to age-matched control values. Our results indicate that microglia may be recruited to participate in the modulation of neuronal structural remodeling during developmental critical periods and in response to alteration in sensory input.

Synergistic Transcriptional Changes in AMPA and GABAA Receptor Genes Support Compensatory Plasticity Following Unilateral Hearing Loss

Debilitating perceptual disorders including tinnitus, hyperacusis, phantom limb pain and visual release hallucinations may reflect aberrant patterns of neural activity in central sensory pathways following a loss of peripheral sensory input. Here, we explore short- and long-term changes in gene expression that may contribute to hyperexcitability following a sudden, profound loss of auditory input from one ear. We used fluorescence in situ hybridization to quantify mRNA levels for genes encoding AMPA and GABAA receptor subunits (Gria2 and Gabra1, respectively) in single neurons from the inferior colliculus (IC) and auditory cortex (ACtx). Thirty days after unilateral hearing loss, Gria2 levels were significantly increased while Gabra1 levels were significantly decreased. Transcriptional rebalancing was more pronounced in ACtx than IC and bore no obvious relationship to the degree of hearing loss. By contrast to the opposing, synergistic shifts in Gria2 and Gabra1 observed 30 days after hearing loss, we found that transcription levels for both genes were equivalently reduced after 5 days of hearing loss, producing no net change in the excitatory/inhibitory transcriptional balance. Opposing transcriptional shifts in AMPA and GABA receptor genes that emerge several weeks after a peripheral insult could promote both sensitization and disinhibition to support a homeostatic recovery of neural activity following auditory deprivation. Imprecise transcriptional changes could also drive the system toward perceptual hypersensitivity, degraded temporal processing and the irrepressible perception of non-existent environmental stimuli, a trio of perceptual impairments that often accompany chronic sensory deprivation.

Hearing Loss and Ethnicity in Age-related Cognitive Decline

Hearing Loss and Ethnicity in Age-related Cognitive Decline

Experience-dependent regulation of tissue-type plasminogen activator in the mouse barrel cortex

It has been suggested that tissue-type plasminogen activator (tPA), a serine protease, plays a key role in regulating the extracellular matrix core proteins, thereby impacting the structural plasticity in the cerebral cortex. Much is known about its role in regulating plasticity in the visual cortex. However, its permissive role has not been demonstrated to generalize to other cerebral cortical areas. By utilizing a combination of immunofluorescent histochemistry and confocal microscopy, we demonstrate that endogenous tPA is indeed present in the somatosensory cortex, and its expression is experience-dependent. Chronic sensory deprivation induced by whisker trimming from birth for one month leads to increased tPA immunoreactivity in all layers of the barrel cortex. Furthermore, tPA immunoreactivity remains high even after sensation has been restored to the mystacial pad (by allowing whiskers to grow back to full length for one month). Our results suggest that tPA levels in the cerebral cortex are regulated by sensory experience, and play a key role in regulating structural remodeling in the cerebral cortex.

All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation

We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain.

The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex.

Switch time-point for rapid experience-dependent changes in zinc-containing circuits in the mouse barrel cortex

It has been previously demonstrated that in the mouse barrel cortex, synaptic zinc is regulated by sensory experience. In adult mice, cutting selected vibrissae produced a rapid but transient elevation of synaptic zinc in the corresponding barrels several hours later, whereas in 8 day-old animals this procedure did not affect synaptic zinc. In the present study, we wished to determine the postnatal age at which zinc-containing terminals gain the ability to respond rapidly to a restriction of sensory input. We therefore examined the effects of 1-day sensory deprivation starting at different postnatal ages. For this purpose we unilaterally trimmed all rows of vibrissae, except for row C, and we then visualized synaptic zinc in the barrel cortex 24 h later. Up to postnatal day 15 such procedure had no effect on the level of synaptic zinc. However, beginning at postnatal day 16, 1-day sensory deprivation produced an increase in synaptic zinc within hollows of deprived rows of barrels as compared to non-deprived rows. These results show that during development there is a specific time-point after which zinc-containing circuits may respond rapidly to altered sensory inputs. A comparison of these findings with previous results obtained after chronic sensory deprivation suggests that a specific time window exists in development for persistent alterations in zinc-containing circuits.

Differential response of synaptic zinc levels to sensory deprivation in the barrel cortex of young and adult mice

The distribution of synaptic zinc after short-term (up to 48 h) tactile deprivation of vibrissae was investigated in the barrel cortex of mice using histochemical staining. In adult mice, 12 h after trimming selected rows of vibrissae, an increase in zinc staining in the deprived barrels was observed. This increase was still present 48 h after trimming. These results indicate that the level of synaptic zinc is rapidly regulated by neuronal activity in adult mice. In young (8-day-old) mice, the short-term deprivation did not alter zinc staining and only chronic sensory deprivation produced an increase in zinc staining. However, after long-term deprivation no changes were found in adult mice. These results suggest that different mechanisms might be involved in functional reorganization of zinc containing terminals in young and fully mature cerebral cortex.

Evidence for Physiological Down-regulation of Brain Oxidative Phosphorylation in Alzheimer's Disease

In vivoimaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain. Indeed, the pattern of down-regulation of expression for both mitochondrial and nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer brain resembles the pattern of down-regulation in normal brain caused by chronic sensory deprivation. In both cases, down-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors. Physiological down-regulation of OXPHOS gene expression in Alzheimer's is consistent with PET evidence that cognitive or psychophysical activation of mildly to moderately demented Alzheimer's patients can augment brain–blood flow and glucose metabolism to the same extent as in control subjects. If the primary neuronal defect that leads to reduced brain energy demand in Alzheimer's disease could be prevented or treated, brain glucose transport and OXPHOS enzyme activities might recover to normal levels.

Chronic sensory deprivation affects cytochrome oxidase staining and glutamic acid decar☐ylase immunoreactivity in adult rat ventrobasal thalamus

The rodent ventrobasal thalamus (VB) contains groups of vibrissa-related neurons (barreloids) that are highly reactive for the enzyme cytochrome oxidase. The present experiments show that each barreloid also contains a dense accumulation of glutamic acid decar☐ylase (GAD) immunoreactive terminals. Chronic vibrissa trimming results in parallel declines in staining for both cytochrome oxidase (CO) and GAD in barreloids associated with the trimmed hairs. Thus, thalamic metabolism like that in the cortex is dependent upon normal sensory input. This includes projection neurons as well as neurons in the reticular nucleus, which are the major source of γ-aminobutyric acid (GABA)ergic input to the rat VB.

Dendritic sprouting and compensatory synaptogenesis in an identified interneuron follow auditory deprivation in a cricket.

We examined the effect of chronic afferent deprivation on an identified interneuron (Int-1) in the auditory system of the Australian field cricket Teleogryllus oceanicus. In normal intact crickets, the auditory afferents from each ear terminate ipsilaterally onto a single Int-1. Each bilaterally paired Int-1 is excited by ultrasound stimulation of its ipsilateral ear but not by the contralateral ear. Unilateral removal of an ear early in postembryonic development deprives the developing Int-1 of ipsilateral auditory innervation. Consequently, the ipsilateral dendrites of the deprived interneuron sprout, grow aberrantly across the ganglionic midline, and terminate specifically in the intact auditory neuropile of the contralateral (unlesioned) side, where they form functional synapses with the contralateral afferents. This unusual compensatory dendritic sprouting restores auditory function to the neuron. Thus, it is demonstrated that the dendritic shape of an identified Int, as well as its synaptic connectivity, is altered as a consequence of chronic sensory deprivation.

The effects of chronic sensory deprivation on language and comprehension

The effects of chronic sensory deprivation on language and comprehension