Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus

Brain Struct Funct. 2015 Jul;220(4):2027-42. doi: 10.1007/s00429-014-0768-y. Epub 2014 Apr 19.

Abstract

The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1
  • Animals
  • Astrocytes / physiology*
  • Astrocytes / ultrastructure
  • Bromodeoxyuridine / metabolism
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Neurogenesis / drug effects
  • Neurogenesis / genetics
  • Neurons / cytology*
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Phosphopyruvate Hydratase / metabolism
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • S100 Calcium Binding Protein beta Subunit / metabolism
  • Synapses / physiology
  • Synapses / ultrastructure
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics

Substances

  • Aldehyde Dehydrogenase 1
  • Glial Fibrillary Acidic Protein
  • Isoenzymes
  • S100 Calcium Binding Protein beta Subunit
  • Green Fluorescent Proteins
  • dihydrokainic acid
  • Aldh1 protein, mouse
  • Retinal Dehydrogenase
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine
  • Kainic Acid