Low excitatory innervation balances high intrinsic excitability of immature dentate neurons.
Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spike due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.
Department of Neurobiology and Evelyn McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.|Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, Perugia 06126, Italy.
Cristina V
CV
Dieni
Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, Perugia 06126, Italy.
Roberto
R
Panichi
Data-driven and Neural Computing Department, Sandia National Laboratories, Albuquerque, New Mexico 87185, USA.
James B
JB
Aimone
Department of Cell Biology and Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Chay T
CT
Kuo
Department of Neurobiology and Evelyn McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Jacques I
JI
Wadiche
Department of Neurobiology and Evelyn McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Linda
L
Overstreet-Wadiche
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008867:Microtomy; D016202:N-Methylaspartate / Q000494:pharmacology; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D046509:Tissue Culture Techniques; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
C577485:Nes protein, mouse; D064231:Nestin; D011724:Pyridazines; D013629:Tamoxifen; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C049853:gabazine; C045073:Cre recombinase; D019426:Integrases