Genetically increased cell-intrinsic excitability enhances neuronal integration into adult brain circuits.
New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.
Lin
Chia-Wei
CW
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sim
Shuyin
S
Ainsworth
Alice
A
Okada
Masayoshi
M
Kelsch
Wolfgang
W
Lois
Carlos
C
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002470:Cell Survival; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels