recording-spatially-restricted-oscillations-hippocampus-behaving

Recording Spatially Restricted Oscillations in the Hippocampus of Behaving Mice

The local field potential (LFP) emerges from ion movements across neural membranes. Since the voltage recorded by LFP electrodes reflects the summed ...

University of Freiburg

Most GABAergic interneurons in the cortex are born at embryonic stages in the ganglionic eminences and migrate tangentially to their final destination. They continue, however, to differentiate and functionally integrate in the circuitry until later postnatal stages of the rodent brain. Recent investigations show that interneurons undergo marked changes in their morphological, intrinsic and synaptic properties as they mature. Action potential shape and its propagation, the period of transmitter release and the time course of the postsynaptic GABA(A)  receptor-mediated conductance become faster during the first three to four postnatal weeks, resulting in a developmental switch of interneurons from slow to fast signalling units. At the same time, the nature of GABAergic signalling is classically considered to shift from depolarizing to hyperpolarizing. However, recent studies oppose this view as interneuron synapses can be shunting, excitatory or hyperpolarizing in the mature cortex, demonstrating the coexistence of diverse developmental rules for the emerging effects of GABAergic synapses. Thus, mature interneuron signalling comes in many forms and is apparently optimized to the network in which the neurons are embedded.

Postnatal differentiation of cortical interneuron signalling.

Alzheimer's disease (AD) is characterized by severe neuronal loss as well as the accumulation of amyloid-β (Aβ), which ultimately leads to plaque formation. Although there is now a general agreement that the aggregation of Aβ can be initiated by prion-like seeding, the impact and functional consequences of induced Aβ deposits (Aβ seeding) on neurons still remain open questions. Here, we find that Aβ seeding, representing early stages of plaque formation, leads to a dramatic decrease in proliferation and neurogenesis in two APP transgenic mouse models. We further demonstrate that neuronal cell death occurs primarily in the vicinity of induced Aβ deposits culminating in electrophysiological abnormalities. Notably, environmental enrichment and voluntary exercise not only revives adult neurogenesis and reverses memory deficits but, most importantly, prevents Aβ seeding by activated, phagocytic microglia cells. Our work expands the current knowledge regarding Aβ seeding and the consequences thereof and attributes microglia an important role in diminishing Aβ seeding by environmental enrichment.

Article	Year
Postnatal differentiation of cortical interneuron signalling. The European journal of neuroscience\| PubMed ID: 22103425	2011
Seed-induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease. The EMBO journal\| PubMed ID: 29229786	2018

Jonas-Frederic Sauer

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