scholarly journals Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis

2020 ◽  
Vol 133 (20) ◽  
pp. jcs243972
Author(s):  
So-Hee Lim ◽  
Sangyep Shin ◽  
Myoung-Hwan Kim ◽  
Eung Chang Kim ◽  
Da Yong Lee ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Tyrosine Phosphorylation ◽  
Hippocampal Neurons ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Hippocampal Neurogenesis ◽  
Wild Type ◽  
Synaptic Functions ◽  
Term Potentiation ◽  
Deficient Mice

ABSTRACTPTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT−/− null and PTPRT-D401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant–dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder.

scholarly journals Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Kreis ◽  
Jana Desloovere ◽  
Nuria Suelves ◽  
Nathalie Pierrot ◽  
Xavier Yerna ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Neuronal Loss ◽  
Gaba Release ◽  
Long Term Potentiation ◽  
Precursor Protein ◽  
Wild Type ◽  
Inhibitory Neurotransmission ◽  
Gaba Production ◽  
Synaptic Functions ◽  
Term Potentiation

AbstractThe function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product amyloid beta (Aβ) together with neurofibrillary tangles constitute the hallmarks of Alzheimer’s disease (AD). Yet, imbalance of excitatory and inhibitory neurotransmission accompanied by loss of synaptic functions, has been reported much earlier and independent of any detectable pathological markers. Recently, soluble APP fragments have been shown to bind to presynaptic GABAB receptors (GABABRs), subsequently decreasing the probability of neurotransmitter release. In this body of work, we were able to show that overexpression of wild-type human APP in mice (hAPPwt) causes early cognitive impairment, neuronal loss, and electrophysiological abnormalities in the absence of amyloid plaques and at very low levels of Aβ. hAPPwt mice exhibited neuronal overexcitation that was evident in EEG and increased long-term potentiation (LTP). Overexpression of hAPPwt did not alter GABAergic/glutamatergic receptor components or GABA production ability. Nonetheless, we detected a decrease of GABA but not glutamate that could be linked to soluble APP fragments, acting on presynaptic GABABRs and subsequently reducing GABA release. By using a specific presynaptic GABABR antagonist, we were able to rescue hyperexcitation in hAPPwt animals. Our results provide evidence that APP plays a crucial role in regulating inhibitory neurotransmission.

Enhanced long-term potentiation in vivo in dentate gyrus of NELL2-deficient mice

Neuroreport ◽  
2004 ◽  
Vol 15 (3) ◽  
pp. 417-420 ◽  
Author(s):  
Shogo Matsuyama ◽  
Koutoku Aihara ◽  
Naoki Nishino ◽  
Satoshi Takeda ◽  
Katsuyuki Tanizawa ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Deficient Mice

Increased network excitability and impaired induction of long-term potentiation in the dentate gyrus of collybistin-deficient mice in vivo

2009 ◽  
Vol 41 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Peter Jedlicka ◽  
Theofilos Papadopoulos ◽  
Thomas Deller ◽  
Heinrich Betz ◽  
Stephan W. Schwarzacher
Keyword(s):  
Dentate Gyrus ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Deficient Mice

Lack of expression of long-term potentiation in the dentate gyrus but not in the CA1 region of the hippocampus of μ-opioid receptor-deficient mice

2000 ◽  
Vol 39 (6) ◽  
pp. 952-960 ◽  
Author(s):  
Henry Matthies ◽  
Helmut Schroeder ◽  
Axel Becker ◽  
Horace Loh ◽  
Volker Höllt ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Opioid Receptor ◽  
Long Term Potentiation ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Μ Opioid Receptor ◽  
Deficient Mice

In Vivo Recordings of Long-Term Potentiation and Long-Term Depression in the Dentate Gyrus of the Neonatal Rat

2004 ◽  
Vol 91 (2) ◽  
pp. 613-622 ◽  
Author(s):  
Michael P. O'Boyle ◽  
Viet Do ◽  
Brian E. Derrick ◽  
Brenda J. Claiborne
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Neonatal Rat ◽  
Perforant Path ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Old Rats

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist ( R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.

Attenuated LTP in Hippocampal Dentate Gyrus Neurons of Mice Deficient in the PAF Receptor

2001 ◽  
Vol 85 (1) ◽  
pp. 384-390 ◽  
Author(s):  
Chu Chen ◽  
Jeffrey C. Magee ◽  
Victor Marcheselli ◽  
Mattie Hardy ◽  
Nicolas G. Bazan
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Wild Type ◽  
In The Wild ◽  
Paf Receptor ◽  
Deficient Mice

Platelet-activating factor (PAF), a bioactive lipid (1- O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A2and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 ± 14%, mean ± SE; n = 32) when compared with that in wild-type mice (219 ± 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 μM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 μM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.

scholarly journals Impaired long-term potentiation induction in dentate gyrus of calretinin-deficient mice

1997 ◽  
Vol 94 (19) ◽  
pp. 10415-10420 ◽  
Author(s):  
S. Schurmans ◽  
S. N. Schiffmann ◽  
H. Gurden ◽  
M. Lemaire ◽  
H.-P. Lipp ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Deficient Mice
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