Abstract
The transcription factor Foxg1 is known to be continuously expressed at a high level in mature neurons in the telencephalon, but little is known about its role in neural plasticity. Mutations in human FOXG1 cause deficiencies in learning and memory and limit social ability, which is defined as FOXG1 syndrome, but its pathogenic mechanism remains unclear. To examine the role of Foxg1 in adults, we crossed Camk2a-CreER with Foxg1fl/fl mice and conditionally disrupted Foxg1 with tamoxifen in mature neurons. We found that spatial learning and memory were significantly impaired when examined by the Morris water maze test. The cKO mice also showed a significant reduction in freezing time during the contextual and cued fear conditioning test, indicating that fear conditioning memory was affected. A remarkable reduction in Schaffer-collateral long-term potentiation was also recorded. Morphologically, the dendritic arborization and spine densities of hippocampal pyramidal neurons were significantly reduced. Primary cell culture further confirmed altered dendritic complexity after Foxg1 deletion. Our results indicated that Foxg1 plays an important role in maintaining the neural plasticity, which is vital to high-grade function.
Highlights
Most neurons have several dendrites that function as information inputs and single axons that serve as information outputs [1]
Loss of Foxg1 leads to deficiency in social and cognitive behaviors Patients suffering from FOXG1 syndrome exhibit mental retardation, absence of social ability and intellectual disabilities [21]
To explore the cellular basis underlying the symptoms and to investigate the function of Foxg1 in telencephalic mature neurons, Foxg1 was deleted by crossing Foxg1fl/fl with a Camk2a-CreER line combined with tamoxifen induction
Summary
Most neurons have several dendrites that function as information inputs and single axons that serve as information outputs [1]. Primary dendrites are derived from the cell body and branch to form complicated secondary and tertiary dendrites [2]. Dendrite arbors are highly dynamic, extending and retracting branches as maturation proceeds. The size and shape of a neuron’s dendrite arbor are critical for the determination of the number and distribution of receptive synaptic contacts [3]. Spines are small protrusions that are derived from dendrites and harbor the majority of glutamatergic excitatory synapses in the mammalian forebrain [4, 5]. Dendritic spines undergo experience-dependent morphological changes, and even subtle changes in dendritic spines may have marked
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