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

Abstract

Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is a process regulated by experience. To understand whether experience also modifies the connectivity of new neurons, we systematically investigated changes in their innervation following environmental enrichment (EE). We found that EE exposure between 2-6 weeks following neuron birth, rather than merely increasing the number of new neurons, profoundly affected their pattern of monosynaptic inputs. Both local innervation by interneurons and to even greater degree long-distance innervation by cortical neurons were markedly enhanced. Furthermore, following EE, new neurons received inputs from CA3 and CA1 inhibitory neurons that were rarely observed under control conditions. While EE-induced changes in inhibitory innervation were largely transient, cortical innervation remained increased after returning animals to control conditions. Our findings demonstrate an unprecedented experience-dependent reorganization of connections impinging onto adult-born neurons, which is likely to have important impact on their contribution to hippocampal information processing.

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

“…While Ugolini (1995) observed a direct correlation between the speed of transsynaptic transmission of CVS RABV and the strength of the inputs, the results of recent in vitro experiments with G RABV in the presence or absence of various inhibitors of neuronal activity like tetrodotoxin (TTX) and Bicucullin, or receptor-blocking molecules like AP5 and NBQX, or blocking SNARE-dependent neurotransmitter release per se does not significantly change rabies spread (Arenkiel et al, 2011;Bergami et al, 2015;Deshpande et al, 2013). This indicates that at-the-time activity of synapses is not a fundamental prerequisite for RABV spread and argues against an influence of synaptic activity on transsynaptic transfer of the virus.…”

“…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.…”

“…This indicates that at-the-time activity of synapses is not a fundamental prerequisite for RABV spread and argues against an influence of synaptic activity on transsynaptic transfer of the virus. The observed enhanced experience-or stimulus-dependent transsynaptic labeling may thus be rather attributable to changes in the number of synaptic inputs per cell or structural features of the synapse (Arenkiel et al, 2011;Bergami et al, 2015).…”

Retroviral induction of GSK-3β expression blocks the stimulatory action of physical exercise on the maturation of newborn neurons

“…Finally, all mice were killed 4 weeks after retroviral injections. The 2-week post-injection interval was selected as the starting point of physical exercise training, given that the period of maximal responsiveness of newborn neurons to the effects of this stimulus and also to environmental enrichment begins at this cell age [25].…”

Effects of 915 MHz Radiofrequency Identification Electromagnetic Field Exposure on Neuronal Precursor Cells in the Dentate Gyrus of Adult Rat Brains

“…Developing nervous cells can be altered by various factors such as disease, drug [7], diet [8], exercise [6], and aging [9]. The electromagnetic spectrum extends from below the low-frequencies used for radio communication to gamma radiation within the short-wavelength region.…”