Abstract
Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render cortical modules more sensitive to stimulation and once activated, more autonomous, isolated, and more difficult to command. This could underlie some of the core symptoms observed in humans prenatally exposed to valproic acid.
| Original language | English |
|---|---|
| Book series | Cerebral cortex (New York, N.Y. : 1991) |
| Volume | 18 |
| Issue number | 4 |
| Pages (from-to) | 763-70 |
| Number of pages | 8 |
| DOIs | |
| Publication status | Published - Apr 2008 |
Keywords
- Animals
- Anticonvulsants
- Autistic Disorder
- Cell Count
- Disease Models, Animal
- Female
- Male
- Neocortex
- Neural Pathways
- Organ Culture Techniques
- Patch-Clamp Techniques
- Pregnancy
- Prenatal Exposure Delayed Effects
- Pyramidal Cells
- Rats
- Rats, Wistar
- Valproic Acid