July 31, 2013. Where a cortical interneuron is born determines what glutamate receptor subunits it expresses, reports a new study published online July 14, 2013, in Nature Neuroscience and led by Kenneth Pelkey, of the National Institute of Child Health and Human Development in Bethesda, Maryland.
A wide variety of interneurons, the inhibitory cells that help to shape and synchronize excitatory principal cell firing, are found throughout the cortex and hippocampus and fall into distinct categories based on their morphological, electrophysiological, and molecular properties (Ascoli et al., 2008). Subtypes of interneurons also differ in their location of origin. For example, parvalbumin- and somatostatin-containing populations derive from progenitor cells in the medial ganglionic eminence (MGE) of the ventral telencephalon, while those expressing calretinin, reelin, and cholecystokinin hail from cells in the caudal ganglionic eminence (CGE).
Proper interneuron integration into cortical circuits depends on appropriate glutamate receptor expression. In fact, mouse models that disrupt NMDA and AMPA receptors located on specific interneuron populations produce abnormal cortical synchrony and reproduce some of the symptoms of schizophrenia (see SRF related news story; SRF news story). To investigate the synaptic development of mouse hippocampal interneurons, first author Jose Matta and colleagues recorded from cells in two different reporter lines of fluorescently labeled MGE- and CGE-derived cells.
The researchers found developmental differences in NMDA and AMPA receptor composition between MGE- and CGE-derived cells. Specifically, by examining the current flow through the cells, they found that the synapses of MGE-derived interneurons relied on AMPA receptors that lacked GluA2 subunits, while those from CGE-originating interneurons used AMPA receptors that included GluA2 subunits. CGE-derived interneurons depended more on NMDA receptor-mediated current than did MGE-derived cells. While cells from the CGE expressed NR2B-containing NMDA receptors across the lifespan, cells from the MGE (including the parvalbumin cells thought to be most affected in schizophrenia) underwent a NR2B-to-NR2A switch between neonatal and juvenile time periods, and this flip could be prompted by repetitive synaptic activity.
The results establish developmental origin-regulated rules of synaptic integration for interneurons, said the authors, and “may relate to observations that early, but not late, postnatal disruption of excitatory synaptic input to specific interneuron cohorts can precipitate neurological disorders such as schizophrenia.”—Allison A. Curley.
Matta JA, Pelkey KA, Craig MT, Chittajallu R, Jeffries BW, McBain CJ. Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity. Nat Neurosci . 2013 Aug ; 16(8):1032-41. Abstract