Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

Abstract

Rabies virus (RABV) is a neurotropic virus exclusively infecting neurons in the central nervous system. RABV encodes five proteins. Among them, the viral glycoprotein (RVG) plays a key role in viral entry into neurons and rabies pathogenesis. It was shown that the nature of the C-terminus of the RABV G protein, which possesses a PDZ binding motif (PBM) modulates the virulence of the RABV strain. The neuronal protein partners recruited by this PBM may alter host cell function. This study was conducted to investigate the effect of RVG on synaptic function in the hippocampal dentate gyrus (DG) of rat.Two μl (10 8 T.U. /ml) of the lentiviral vector containing RVG gene was injected into the DG of rat hippocampus. After 2 weeks, the rat's brain was cross-sectioned and RVG-expressing cells were detected by fluorescent microscopy. Hippocampal synaptic activity of the infected rats was then examined by recording the local field potentials from DG after stimulation of the perforant pathway. Short term synaptic plasticity was also assessed by double pulse stimulation.Expression of RVG in DG increased long term potentiation population spikes (LTP-PS), whereas no facilitation of LTP-PS was found in neurons expressing ∆RVG (deleted PBM). Furthermore, RVG and ∆RVG strengthened paired pulse facilitation.Our data demonstrate that RVG expression facilitates both short and long term synaptic plasticity in the DG indicating that it may involve both pre-and post-synaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

“…In agreement with this proposal, a recent study showed that a peptide derived from RVG, which contains a snake toxin-like sequence, changes synaptic transmissions and motor behavior through blocking acetylcholine receptors (Hueffer et al, 2017). In addition, we recently showed that RVG strengthens both short-and longterm synaptic plasticity in the hippocampal dentate gyrus suggesting that it may alter synaptic function through both pre-and postsynaptic mechanisms (Ghassemi et al, 2021). In line with theses evidences, we found in the present study that RVG expression in the dorsal hippocampus facilitates spatial learning and memory.…”

“…This suggestion is supported by numerous reports indicating modulation of synaptic transmission by RABV including ion channel dysfunction (Iwata et al, 1999), aberrant neurotransmission (Ceccaldi et al, 1993;Dumrongphol et al, 1996;Ladogana et al, 1994), and changes in the electroencephalography of rabies patients (Gourmelon et al, 1991). Furthermore, in the previous study we showed that lentiviral expression of the rabies glycoprotein enhances synaptic transmission in the hippocampal dentate gyrus region (Ghassemi et al, 2021). Another clue that strengthens changes in synaptic function by RABV is that RABV increases release of neurotransmitters including serotonin and catecholamines in the hippocampus of the infected mice for a period of 1 week after infection with a peak on the day 3 (Fu and Jackson, 2005).…”

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

“…The neural protein partners recruited by PBM may change the function of host cells. Ghassemi et al [65] believed that the expression of RABV G promoted both short-and long-term synaptic plasticity in the hippocampal dentate gyrus (DG), suggesting that it may involve presynaptic and postsynaptic mechanisms to alter synaptic function.…”

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

“…In vivo field potentials were recorded according the previously established method 30 . In order to record from DG, a bipolar stimulating electrode (A-M Systems, USA) was implanted at the perforant path (AP: 8.1 from bregma, ML: 4.3 from bregma, DV: 3.3 from dura), and a monopolar electrode was fixed at DG stratum granulosum (AP: 3.8 from bregma, ML: 2.4 from bregma, DV: 3–3.5 from dura) as recording electrode.…”

“…The optimum stimulus was applied every 5 min for 30 min to record baseline synaptic activity. For inducing long term potentiation (LTP), a HFS, consisting of 10 trains of 20 pulses at 400 Hz for DG 30 , 31 and at 200 Hz for CA1 32 , with 80% of maximum intensity was delivered every 10 s, (Fig. 1 ).…”