title: Maturation of a recurrent excitatory neocortical circuit by experience-dependent unsilencing of newly formed dendritic spines.
abstract: Local recurrent excitatory circuits are ubiquitous in neocortex, yet little is known about their development or architecture. Here we introduce a quantitative technique for efficient single-cell resolution circuit mapping using 2-photon (2P) glutamate uncaging and analyze experience-dependent neonatal development of the layer 4 barrel cortex local excitatory circuit. We show that sensory experience specifically drives a 3-fold increase in connectivity at postnatal day (P) 9, producing a highly recurrent network. A profound dendritic spinogenesis occurs concurrent with the connectivity increase, but this is not experience dependent. However, in experience-deprived cortex, a much greater proportion of spines lack postsynaptic AMPA receptors (AMPARs) and synaptic connectivity via NMDA receptors (NMDARs) is the same as in normally developing cortex. Thus we describe a approach for quantitative circuit mapping and show that sensory experience sculpts an intrinsically developing template network, which is based on NMDAR-only synapses, by driving AMPARs into newly formed silent spines.
authors.affiliation: Developmental Synaptic Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. m.c.ashby@bristol.ac.uk
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ashby
authors.forename: John T R
authors.initials: JT
authors.lastname: Isaac
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009415:Nerve Net / Q000254:growth & development*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D011336:Probability; D012683:Sensory Deprivation / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology* / Q000254:growth & development
chemical_list: D018698:Glutamic Acid