Priming of LTP in amygdala and hippocampus by prior paired pulse facilitation paradigm in mice lacking brain serotonin

Abstract

This study focuses on analyzing long‐term potentiation (LTP) changes in the lateral nucleus of the amygdala (LA) and in the CA1 region of the hippocampus in slices derived from mice deficient in tryptophan hydroxylase 2 (TPH2−/−), the rate‐limiting enzyme for 5‐HT synthesis in the brain. We found a reduced LTP in both brain structures in TPH2−/− mice. However, we found no changes in the magnitude of LTP in TPH2−/− mice compared to wildtype mice when it was preceded by a paired pulse protocol. Whereas the magnitude of long‐term depression (LTD) did not differ between wildtype and TPH2−/− mice, priming synapses by LTD‐induction facilitated subsequent CA1‐LTP in wildtype mice to a greater extent than in TPH2−/− mice. In the LA we found no differences between the genotypes in this protocol of metaplasticity. These data show that, unlike exogenous 5‐HT application, lack of 5‐HT in the brain impairs cellular mechanisms responsible for induction of LTP. It is supposed that suppression of LTP observed in TPH2−/− mice might be compensated by mechanisms of metaplasticity induced by paired pulse stimulation or low frequency stimulation before the induction of LTP.

Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

“…In this situation, two action potentials in the presynaptic cell produce two excitatory postsynaptic potentials (EPSPs) in the postsynaptic cell: the first action potential produces the first EPSP, but the second action potential produces an EPSP that is larger than the EPSP produced by the first. PPF modulation therefore highlights a modulation in presynaptic neurotransmitter release [ 34 ]. Using this readout as a proxy for presynaptic function, we observed a significant decrease in PPF in shFERMT2-infected mice compared to shNT-infected control mice (Fig.…”

Alzheimer’s genetic risk factorFERMT2(Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

“…In this situation, two action potentials in the presynaptic cell produce two excitatory postsynaptic potentials (EPSPs) in the postsynaptic cell: the first action potential produces a first EPSP, but the second action potential produces an EPSP that is larger than the EPSP produced by the first. PPF modulation therefore highlights a modulation in presynaptic neurotransmitter release (Gebhardt et al 2019). Using this read-out as a proxy for presynaptic function, we observed a significant decrease in PPF in shFERMT2-infected mice compared to shNTinfected control mice (Fig.…”

A New Perspective on Hippocampal Synaptic Plasticity and Post-stroke Depression

“…This suggests that 5-HT-dependent neurotransmission can modulate hippocampal synaptic plasticity and promote hippocampal neuronal activity to improve depressive behavior. Tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for 5-HT synthesis, has been found to increase depressive behavior in Tph2 knockout mice, whereas deletion of this synthase impairs synaptic plasticity and LTP in the hippocampus (Gebhardt et al 2019;Jacobsen et al 2012). These findings suggest that 5-HT deficiency may induce depressive behavior by inhibiting hippocampal LTP.…”