Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus

Abstract

New neurons, which have been implicated in pattern separation, are continually generated in the dentate gyrus in the adult hippocampus. Using a genetically modified rabies virus, we demonstrated that molecular layer perforant pathway (MOPP) cells innervated newborn granule neurons in adult mouse brain. Stimulating the perforant pathway resulted in the activation of MOPP cells before the activation of dentate granule neurons. Moreover, activation of MOPP cells by focal uncaging of glutamate induced strong inhibition of granule cells. Together, these results indicate that MOPP cells located in the molecular layer of the dentate gyrus contribute to feed-forward inhibition of granule cells via perforant pathway activation.adult neurogenesis | interneuron

A Critical Period for Experience-Dependent Remodeling of Adult-Born Neuron Connectivity

“…After having confirmed that neuronal activity does not directly affect the transsynaptic spread of RABV (see Supplemental Experimental Procedures and Figure S1 available online) (Ugolini, 2011), thus validating a dual virus-based monosynaptic tracing technique for detecting changes in connectivity patterns (Deshpande et al, 2013;Li et al, 2013;Vivar et al, 2012), we exposed adult mice to a 4-week-long period of EE ( Figure S2A) and examined the resulting alterations in the spectrum of presynaptic inputs impinging onto adult-generated DG granule neurons. To this end, a GFP-encoding, EnvA-pseudotyped DG RABV (Wickersham et al, 2007) was delivered to the DG of adult mice at different times following infection with a G-TVA retrovirus encoding (1) the EnvA receptor (TVA) for restricting primary RABV infection to newborn neurons as ''starter'' population and (2) the RABV glycoprotein (G), which is necessary for subsequent monosynaptic transfer (via transcomplementation) to their first-order presynaptic partners ( Figure 1A).…”

G gene-deficient single-round rabies viruses for neuronal circuit analysis

“…A fundamental difference between lentiviruses and (onco-) retroviruses like mouse leukemia virus (MLV) is the inability of the latter to transduce postmitotic cells like neurons. This selective restriction to infection of dividing cells was elegantly exploited in studies on adult neurogenesis, assessing the fate of neuronal progenitors and their synaptic integration (Bergami et al, 2015;Deshpande et al, 2013;Li et al, 2013;Vivar et al, 2012). In these studies, MLV expressing RABV G/TVA/dsRed was first used for injection into the subventricular zone of mice brains to transduce dividing neuronal progenitors.…”

“…Stereotaxic injection of a lentivirus that expressed Cre along with a tdTomato reporter into the rostral migratory stream (RMS) fluorescently labeled adult-born neurons, and the activity of Cre recombinase allowed for expression of TVA and G from the cell genome (Garcia et al, 2014). Li et al (2013) created a mouse line, in which the entire set of the three genes for monosynaptic tracing is controlled by Cre-recombinase activity, Rosa26Lox-stop-LoxHTB (H: histone-tag GFP; T: TVA; B: rabies glycoprotein B19 G). They targeted newborn neurons by utilizing a retroviral vector just expressing Cre-recombinase.…”

Development of glutamatergic innervation during maturation of adult-born neurons

“…Although GABAergic signaling precedes glutamatergic synaptogenesis at the earliest stages of GC maturation, by 4 weeks immature GCs exhibit a lower ratio of inhibitory to excitatory synaptic strength compared to mature GCs (Dieni et al, 2013). The low I/E ratio and the slow rise times of inhibitory synaptic currents result in less functional inhibition of immature GCs relative to mature GCs, contributing to greater activation in response to molecular layer stimulation (Marín-Burgin et al, 2012;Li et al, 2013;Dieni et al, 2013).…”