title: Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment.
abstract: Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants. We studied the development of transplant-derived interneurons and compared it to endogenously developing interneurons (those that are born and develop in the same animal) at parallel developmental time points, using patch-clamp recordings in acute cortical slices. We found that transplant-derived interneurons develop into fast-spiking and non-fast-spiking neurons characteristic of the medial ganglionic eminence (MGE) lineage. Transplant-derived interneurons matured more rapidly than endogenously developing interneurons, as shown by more hyperpolarized membrane potentials, smaller input resistances, and narrower action potentials at a juvenile age. In addition, transplant-derived fast-spiking interneurons have more quickly saturating input-output relationships and lower maximal firing rates in adulthood, indicating a possible divergence in function. Transplant-derived interneurons both form inhibitory synapses onto host excitatory neurons and receive excitatory synapses from host pyramidal cells. Unitary connection properties are similar to those of host interneurons. These transplant-derived interneurons, however, were less densely functionally connected onto host pyramidal cells than were host interneurons and received fewer spontaneous excitatory inputs from host cells. These findings suggest that many physiological characteristics of interneurons are autonomously determined, while some factors impacting their circuit function may be influenced by the environment in which they develop.NEW & NOTEWORTHYTransplanting embryonic interneurons into older brains induces a period of plasticity in the recipient animal. We find that these interneurons develop typical fast-spiking and non-fast-spiking phenotypes by the end of adolescence. However, the input-output characteristics of transplant-derived neurons diverged from endogenously developing interneurons during adulthood, and they showed lower connection rates to local pyramidal cells at all time points. This suggests a unique and ongoing role of transplant-derived interneurons in host circuits, enabling interneuron transplant therapies.
authors.affiliation: Center for Integrative Neuroscience, University of California, San Francisco, California.|Department of Neurology, University of California, San Francisco, California.|Coleman Memorial Laboratory, University of California, San Francisco, California.|Kavli Center for Fundamental Neuroscience, University of California, San Francisco, California.
authors.forename: Phillip
authors.identifier: 0000-0001-5276-5732
authors.initials: P
authors.lastname: Larimer
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California.|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California.
authors.forename: Julien
authors.initials: J
authors.lastname: Spatazza
authors.affiliation: Center for Integrative Neuroscience, University of California, San Francisco, California.|Department of Physiology, University of California, San Francisco, California.|Kavli Center for Fundamental Neuroscience, University of California, San Francisco, California.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Stryker
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California.|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California.
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
authors.affiliation: Center for Integrative Neuroscience, University of California, San Francisco, California; andrea.hasenstaub@ucsf.edu.|Coleman Memorial Laboratory, University of California, San Francisco, California.|Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, California; and.|Kavli Center for Fundamental Neuroscience, University of California, San Francisco, California.
authors.forename: Andrea R
authors.identifier: 0000-0003-3998-5073
authors.initials: AR
authors.lastname: Hasenstaub
mesh_terms: D000200:Action Potentials; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D007395:Interneurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D051379:Mice; D055495:Neurogenesis; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology
keywords: fast-spiking neuron; low-threshold-spiking neuron; medial ganglionic eminence