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Updated: Jun 3, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Early, time-dependent disturbances of hippocampal synaptic transmission and plasticity after in utero immune
Marion Escobar1, Nadine Crouzin, Mélanie Cavalier
1Institut des Biomolécules Max Mousseron, Montpellier, France.
Insights
Prenatal exposure to lipopolysaccharide (LPS) alters brain development, accelerating long-term depression and impairing N-methyl-D-aspartate receptors (NMDArs) in offspring. These early changes may lead to later brain dysfunction.
Area of Science:
- Neuroscience
- Developmental Biology
- Psychiatry
Background:
- Maternal infection during pregnancy is linked to offspring psychiatric and neurologic disorders.
- Prenatal exposure to lipopolysaccharide (LPS) in rats causes behavioral and synaptic deficits in mature offspring.
- The study investigates early-stage alterations in excitatory transmission and plasticity following prenatal LPS exposure.
Purpose of the Study:
- To examine the developmental trajectory of synaptic plasticity in the hippocampus after prenatal LPS exposure.
- To assess the role of N-methyl-D-aspartate receptors (NMDArs) in synaptic transmission during early development in LPS-exposed offspring.
Main Methods:
- Electrophysiological recordings were performed on hippocampal CA1 slices from prenatally LPS-exposed rats (4-190 days old).
- Developmental profiles of long-term depression (LTD) were studied using high-frequency stimulation.
- NMDAr contribution to synaptic transmission and subunit expression (GluN1, GluN2) were analyzed.
Main Results:
- The age-dependent decrease in LTD was accelerated in LPS-exposed animals.
- A transient long-term potentiation, dependent on metabotropic glutamate receptors and protein kinase A, emerged between 16-25 days.
- Prenatal LPS exposure impaired NMDAr development, reducing GluN1 expression without affecting the GluN2 subunit switch.
Conclusions:
- Aberrant synaptic plasticity and NMDAr hypofunction occur early in development following prenatal LPS exposure.
- These early hippocampal alterations may contribute to the development of brain dysfunctions later in life.
Background:
Maternal infection during pregnancy is a recognized risk factor for the occurrence of a broad spectrum of psychiatric and neurologic disorders, including schizophrenia, autism, and cerebral palsy. Prenatal exposure of rats to lipopolysaccharide (LPS) leads to impaired learning and psychotic-like behavior in mature offspring, together with an enduring modification of glutamatergic excitatory synaptic transmission. The question that arises is whether any alterations of excitatory transmission and plasticity occurred at early developmental stages after in utero LPS exposure.
Methods:
Electrophysiological experiments were carried out on the CA1 area of hippocampal slices from prenatally LPS-exposed male offspring from 4 to 190 days old to study the developmental profiles of long-term depression (LTD) triggered by delivering 900 shocks either single- or paired-pulse (50-msec interval) at 1 Hz and the N-methyl-D-aspartate receptor (NMDAr) contribution to synaptic transmission.
Results:
The age-dependent drop of LTD is accelerated in prenatally LPS-exposed animals, and LTD is transiently converted into a slow-onset long-term potentiation between 16 and 25 days old. This long-term potentiation depends on Group I metabotropic glutamate receptors and protein kinase A activations and is independent of NMDArs. Maternal LPS challenge also leads to a rapid developmental impairment of synaptic NMDArs. This was associated with a concomitant reduced expression of GluN1, without any detectable alteration in the developmental switch of NMDAr GluN2 subunits.
Conclusions:
Aberrant forms of synaptic plasticity can be detected at early developmental stages after prenatal LPS challenge concomitant with a clear hypo-functioning of the NMDAr in the hippocampus. This might result in later-occurring brain dysfunctions.
