Functional Connectivity Favors Aberrant Visual Network c-Fos Expression Accompanied by Cortical Synapse Loss in a Mouse Model of Alzheimer's Disease.

Background: While Alzheimer's disease (AD) has been extensively studied with a focus on cognitive networks, visual network dysfunction has received less attention despite compelling evidence of its significance in AD patients and mouse models. We recently reported c-Fos and synaptic dysregulation in the primary visual cortex of a pre-amyloid plaque AD-model.

Objective: We test whether c-Fos expression and presynaptic density/dynamics differ in cortical and subcortical visual areas in an AD-model.

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer's disease.

While Alzheimer's disease (AD) has been extensively studied with a focus on cognitive networks, sensory network dysfunction has received comparatively less attention despite compelling evidence of its significance in both Alzheimer's disease patients and mouse models. We recently found that neurons in the primary visual cortex of an AD mouse model expressing human amyloid protein precursor with the Swedish and Indiana mutations (hAPP mutations) exhibit aberrant c-Fos expression and altered synaptic structures at a pre-amyloid plaque stage. However, it is unclear whether aberrant c-Fos expression and synaptic pathology vary across the broader visual network and to what extent c-Fos abnormality in the cortex is inherited through functional connectivity.

Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes.

Alexander disease (AxD) is a leukodystrophy caused by heterozygous mutations in the gene for glial fibrillary acidic protein, an intermediate filament protein expressed by astrocytes. The mutation causes prominent protein aggregates inside astrocytes; there is also loss of myelin and oligodendrocytes and neuronal degeneration. We show that immunohistochemical staining for glutamate transporter 1, the major brain glutamate transporter expressed primarily in astrocytes suggests decreased levels in the hippocampi of infantile AxD patients.

Microphysiology of epileptiform activity in human neocortex.

The authors report the use of dense two-dimensional microelectrode array recordings to characterize fine resolution electrocortical activity ("microEEG") in epileptogenic human cortex. A 16-mm(2) 96 microelectrode array with 400-mum interelectrode spacing was implanted in five patients undergoing invasive EEG monitoring for medically refractory epilepsy. High spatial resolution data from the array were analyzed in conjunction with simultaneously acquired data from standard intracranial electrode grids and strips.