title: Evidence for Competition for Target Innervation in the Medial Prefrontal Cortex.
abstract: Inputs to sensory cortices are known to compete for target innervation through an activity-dependent mechanism during critical periods. To investigate whether this principle also applies to association cortices such as the medial prefrontal cortex (mPFC), we produced a bilateral lesion during early development to the ventral hippocampus (vHC), an input to the mPFC, and analyzed the intensity of the projection from another input, the basolateral amgydala (BLA). We found that axons from the BLA had a higher density of "en passant" boutons in the mPFC of lesioned animals. Furthermore, the density of neurons labeled with retrograde tracers was increased, and neurons projecting from the BLA to the mPFC showed increased expression of FosB. Since neonatal ventral hippocampal lesion has been used as an animal model of schizophrenia, we investigated its effects on behavior and found a negative correlation between the density of retrogradely labeled neurons in the BLA and the reduction of the startle response in the prepulse inhibition test. Our results not only indicate that the inputs from the BLA and the vHC compete for target innervation in the mPFC during postnatal development but also that subsequent abnormal rewiring might underlie the pathophysiology of neuropsychiatric disorders such as schizophrenia.
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Guirado
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Juzoh
authors.initials: J
authors.lastname: Umemori
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland Current address: Max Planck Institute for Neurobiology, Martinsried, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Sipilä
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Castrén
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000166:cytology* / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology / Q000503:physiopathology; D007051:Ibotenic Acid; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020318:Rats, Long-Evans; D055139:Sensory Gating / Q000502:physiology
chemical_list: C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D007051:Ibotenic Acid
keywords: basolateral amygdala; critical period; medial prefrontal cortex; network; schizophrenia