Adult Neurogenesis Produces Neurons with Unique GABAergic Synapses in the Olfactory Bulb.

Valley MT, Henderson LG, Inverso SA, Lledo PM.
J Neurosci. 2013 Sep 11;33(37):14660-5. PMID:    24027267

Objective:   In adult mammals, interneurons are continuously generated in the olfactory bulb, many of which later become granule cells.  It is known that the immature cells are integrated in to neural circuits and receive inputs that contribute to whether or not they will live or die, but little has been shown about the differences in this fate-deciding process between early and late stages of an organism’s life.  In this paper, it was found that regulation by the GABAB receptor mediated presynaptic regulation is absent in adult-born cells, but not in cells born during neurogenesis.

Results:

·         Recordings from postsynaptic mitral cells (MCs) during photostimulation of channelrhodopsin-expressing presynaptic granule cells (GCs) showed inhibitory post synaptic currents (IPSCs) that could be blocked by GABAA antagonists or application of TTX, suggesting that photostimulation caused GABA release from GCs on to MCs.

·         Application of the GABAB receptor agonist R/S-baclofen caused a decrease in IPSCS caused by photostimulation of early-born GCs, but not in GCs born at postnatal day 60.  They found that GABAB receptor function was not linked to the age of the cell, but rather that aged early-born cells retained receptor function while younger late-born cells did not have GABAB receptor function.

·         After lentiviral expression of markers to differentiate GCs born on p6 and p60, immunoreactivity for the GABAB1 subunit of GABAB was assayed.  P60 GCs had greater dendritic and internal GABAB1, while p6 GCs had greater axonal GABAB1.  This shows that GCs born at different times throughout an animal’s life can have different distribution of the same receptor.

 

Methods:    Mice were anesthetized and their olfactory bulbs were given bilateral injections of lentivirus containing a cassette that had channelrhdopsin2(H134R)eYFP under the control of the synapsin promoter.  After allowing time for gene expression, slices were made from the olfactory bulbs and MCs were held under voltage clamp at +10mV in order to monitor IPSCs.  In animals used for immunohistochemistry, the brain was removed and fixed with 4% paraformaldehyde.

 -DH