Asynchronic transmission in the CA3–CA1 hippocampal synapses in the neurological mutant taiep rat

Abstract

For the taiep rat, a neurological mutant with severe astrogliosis secondary to demyelination, we have described alterations in spinal cord synaptic transmission. Asynchronous responses result from phasic action potential-derived glutamate release in this mutant. To evaluate whether this anomalous transmission is also produced in other regions of the taiep CNS and whether its nature involves a presynaptic or postsynaptic disruption, we studied the CA3-CA1 hippocampal synapses. Excitatory postsynaptic currents (EPSC) evoked by stimulation of Schaffer collaterals were recorded from CA1 pyramidal cells on picrotoxin-treated slices. Initial fast and time-locked EPSCs were evoked by conventional stimulation in both control and taiep neurons, showing similar latency and amplitude values unimodally distributed. In a high percentage of taiep neurons (47%), the initial EPSC was frequently followed by additional asynchronous synaptic currents (EPSC(ASYN)) with latencies ranging from 10 to 300 msec. As with initial EPSCs, EPSC(ASYN) were action potential dependent, sensitive to tetrodotoxin, and blocked by D-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. The occurrence probability of these events decayed monoexponentially as a function of poststimulus time. The elevation of extracellular Ca(2+) induced a reduction of amplitudes and a rate increase of EPSC(ASYN), in parallel with a reduction of paired pulse facilitation of initial EPSCs. The presynaptic fiber volley, extracellularly recorded, showed no significant differences between groups, with similar mean values of area and decay time. These findings in hippocampal circuitry suggest that, in taiep, the asynchronous evoked activity represents a rather generalized phenotype of the glutamatergic synapses and that EPSC(ASYN) seems to be determined by presynaptic alterations.

Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities

“…Importantly, in vitro spinal cord preparations from neonate taiep rats showed delayed maturation of monosynaptic reflexes, with stronger paired pulse depression and delayed posttetanic recovery supporting that demyelination alters electrophysiological responses in central pathways (Fuenzalida, Roncagliolo, Bonansco, & Roncagliolo, 2004). Similarly, in vitro recordings on CA1 pyramidal cells on neonatal taiep hippocampus showed higher asynchrony of monosynaptic responses induced by electrical stimulation of Schaffer collaterals with respect to those obtained in control Sprague-Dawley rats (Bonansco, Fuenzalida, Olivares, Molina, & Roncagliolo, 2007), supporting early developmental electrophysiological alterations on taiep phenotype. However, no additional morphological or behavioral studies on taiep rats have been performed until now.…”

“…These results clearly showed that juvenile taiep rats have altered morphology in the dendrites in the CA1 pyramidal neurons and that these changes did not affect spatial memory as measured using the Morris water maze. In a previous report, using an in vitro neonatal slice hippocampus preparation, pyramidal cells under patch‐clamp recordings, the electrical stimulation of Schaffer collaterals, induced asynchronous monosynaptic glutamatergic transmission (Bonansco et al, ). In the present study, we demonstrated dendritic alterations in some specific areas of the hippocampus that could explain the alterations in information flow.…”

Auditory impairment in H‐ABC tubulinopathy

“…Similar observations have been made for PD (Kuan, Sano, Kaga, Kodama, & Kodama, 2008). In the taiep rat, it has been shown that in the lumbosacral spinal cord (Bonansco, Fuenzalida, & Roncagliolo, 2004), in the optic nerve (Roncagliolo et al, 2006) and in the hippocampus (Bonansco, Fuenzalida, Olivares, Molina, & Roncagliolo, 2007), transmission through synapses is asynchronous. Myelin is traditionally considered fundamental to improve conduction velocity in axons.…”

Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity

“…The procedures of animal care, surgery and slice preparation were in accordance with the guidelines laid down by the Institutional Animal Care and Ethics Committee at the Faculty of Sciences, Universidad de Valparaíso and NIH, USA. The brain slices were obtained as previously described (Bonansco et al. , 2002, 2007; Fuenzalida et al.…”

“…The procedures of animal care, surgery and slice preparation were in accordance with the guidelines laid down by the Institutional Animal Care and Ethics Committee at the Faculty of Sciences, Universidad de Valparaíso and NIH, USA. The brain slices were obtained as previously described (Bonansco et al, 2002(Bonansco et al, , 2007Fuenzalida et al, 2007Fuenzalida et al, , 2009). Coronal hippocampal slices were obtained from Sprague Dawley rats (60 animals; 25-35 days old) after they were anaesthetized with ether and decapitated immediately after the pinch reflex disappeared.…”