Impairment of in vivo theta‐burst long‐term potentiation and network excitability in the dentate gyrus of synaptopodin‐deficient mice lacking the spine apparatus and the cisternal organelle

Abstract

ABSTRACT:The function of the spine apparatus in dendritic spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin 2/2 mice. Here, we used synaptopodin 2/2 mice to explore the role of the spine apparatus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation following theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the spine apparatus and the cisternal organelle leads to a defect in longterm synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. V

Synaptopodin Regulates Plasticity of Dendritic Spines in Hippocampal Neurons

“…These results link activity-dependent increase of SP after LTP-induction (Yamazaki et al, 2001;Fukazawa et al, 2003) and defects of SP-deficient mice in LTP-induction (Deller et al, 2003;Jedlicka et al, 2008a), indicating that SP plays a critical role in NMDA-R dependent increase in GluR1-clusters in individual dendritic spines.…”

“…Studies using mice homozygous for a targeted disruption of the SP gene (SP-deficient mice) indicate that SP plays an important role in the formation of the spine apparatus, because the latter is absent in SP-deficient mice (Deller et al, 2003). These experiments also link SP to the regulation of synaptic plasticity, in that SP-deficient mice demonstrate an impaired ability to express long-term potentiation (LTP) in vitro and in vivo, as well as deficits in spatial memory tasks (Deller et al, 2003;Jedlicka et al, 2008a). By the same token, SP expression is enhanced after tetanic stimulation, an effect that is assumed to underlie a transition from short to long-term potentiation (Yamazaki et al, 2001;Fukazawa et al, 2003).…”

Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus

“…Rneo/+ mice exhibit impaired in vivo synaptic plasticity in the DG In vivo electrophysiological analysis within distinct subregions is an elegant strategy that permits both evaluation of synaptic plasticity together with network properties, where the contribution of the native neuronal circuitry is intact (Bliss et al 2000;Jones et al 2001;Jedlicka et al 2009). Using this approach, we first investigated aspects of short-and long-term plasticity in the hippocampus (Fig.…”

Knockdown of MicroRNA-1 in the Hippocampus Ameliorates Myocardial Infarction Induced Impairment of Long-Term Potentiation

“…For LTP induction, a theta-burst stimulation (TBS) protocol was performed, which comprised six series of six trains of six pulses at 400 Hz, with 200 ms between trains, and 20 s between series, and a pulse width and stimulus intensity that were doubled during the TBS in comparison to baseline recordings. After TBS, the evoked responses were recorded for an additional 60 min (one response per min) [29,30]. …”