Article

Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity. Proc Natl Acad Sci USA

Institut National de la Santé et de la Recherche Médicale U862, Neurocentre Magendie, Glia-Neuron Interactions Group, F33077 Bordeaux, France.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2011; 108(16):6644-9. DOI: 10.1073/pnas.1016928108
Source: PubMed

ABSTRACT

Adult neurogenesis is a process by which the brain produces new neurons once development has ceased. Adult hippocampal neurogenesis has been linked to the relational processing of spatial information, a role attributed to the contribution of newborn neurons to long-term potentiation (LTP). However, whether newborn neurons also influence long-term depression (LTD), and how synaptic transmission and plasticity are affected as they incorporate their network, remain to be determined. To address these issues, we took advantage of a genetic model in which a majority of adult-born neurons can be selectively ablated in the dentate gyrus (DG) and, most importantly, in which neurogenesis can be restored on demand. Using electrophysiological recordings, we show that selective reduction of adult-born neurons impairs synaptic transmission at medial perforant pathway synapses onto DG granule cells. Furthermore, LTP and LTD are largely compromised at these synapses, probably as a result of an increased induction threshold. Whereas the deficits in synaptic transmission and plasticity are completely rescued by restoring neurogenesis, these synapses regain their ability to express LTP much faster than their ability to express LTD. These results demonstrate that both LTP and LTD are influenced by adult neurogenesis. They also indicate that as newborn neurons integrate their network, the ability to express bidirectional synaptic plasticity is largely improved at these synapses. These findings establish that adult neurogenesis is an important process for synaptic transmission and bidirectional plasticity in the DG, accounting for its role in efficiently integrating novel incoming information and in forming new memories.

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    • "The process is essential to normal cognitive function and is widely implicated in disease processes (McEwen, 2006). Neurogenesis in the hippocampal dentate gyrus contributes significantly to central neuroplasticity mechanisms such as long-term potentiation, learning and memory (Massa et al., 2011). Additionally , astrocytes have the ability to eliminate ammonia, and play an important role in the pathogenesis of hepatic encephalopathy (Lockwood et al., 1991; Haussinger et al., 2000). "
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    • "Cognitive deficits constitute a critical pathological feature that is difficult to treat in many psychiatric and neurological disorders, which have been suggested to be associated with impaired adult hippocampal neurogenesis (Leuner et al., 2006; Massa et al., 2011; King et al., 2014). Neurogenesis involves neural precursor cell (NPC) proliferation and differentiation into neurons, a process that has been linked to hippocampal-dependent cognitive processes (Kempermann, 2002; van Praag et al., 2005; Leuner et al., 2006; Deng et al., 2010; Massa et al., 2011). The potential coexistence of impairments in cognitive processes and hippocampal neurogenesis, for example in Alzheimer's disease (Mu and Gage, 2011), Fragile X syndrome (Guo et al., 2012), and mood disorders (Jacobs et al., 2000), raises the possibility that the two are linked. "
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    • "Young (1.5–2 months old) newborn neurons were also shown to be preferentially activated during memory recall in a water maze task, compared to mature neurons, as determined by colabeling of BrdU with immediate early genes such as c- Fos and Arc, in which expression correlates with neuronal firing [48]. Nonetheless, it has only been in the last few years that loss-of-function and gain-of-function approaches with inducible transgenic mice were able to confirm that adult hippocampal neurogenesis is necessary for synaptic transmission and plasticity, including the induction of longterm potentiation (LTP) and long-term depression [49], as well as trace learning in conditioned protocols [50], memory retention in spatial learning tasks [51] [52], and encoding of overlapping input patterns, that is, pattern separation [53]. Adult hippocampal neurogenesis and its functional implications for learning and memory are however influenced negatively by a variety of conditions that are commonly associated with microglial activation and inflammation in the brain, such as chronic stress, aging, and neurodegenerative diseases, as we will review herein. "
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