Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

Abstract

Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit.adult neurogenesis | synaptic tracing | adult neural stem cell | functional integration | pseudotransduction

Neuronal LRP4 regulates synapse formation in the developing CNS

“…5A). Neurons transfected with this vector are susceptible to subsequent infection by the glycoprotein G-deficient, eGFP-encoding EnvApseudotyped rabies virus (RABV) and capable of retrograde transfer of the virus to all immediate presynaptic partners (Deshpande et al, 2013;Wickersham et al, 2007a) (Fig. 5B).…”

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

“…To identify the origin of the presynaptic inputs of adult-born GC spines, we selectively labeled the different glutamatergic cell populations that innervate the GCL. Anatomical and physiological studies have shown that the olfactory cortex (OC), notably the anterior piriform cortex (APC) and the anterior olfactory nucleus (AON), send dense projections back to the OB where they impinge notably onto GCs (18,19,23,24). We injected an adeno-associated virus (AAV) expressing channelrhodopsin-2 (ChR2) fused to the red fluorescent protein mCherry into the APC and AON (Fig.…”

“…Conversely, the selective stimulation of adult-born neurons improves olfactory learning and memory (16), suggesting that these neurons are part of the olfactory memory engram (17). Although recent transsynaptic strategies have revealed the presynaptic connectivity of adult-born neurons (18,19), little is known about how learning affects their structural and synaptic plasticity or which circuits and presynaptic cells are functionally recruited with them during associative learning. By demonstrating that olfactory learning triggers both selective structural rearrangements and changes in synaptic transmission onto adult-born neurons, this study represents a first attempt to link associative learning to functional plasticity of circuits endowed with adult neurogenesis.…”

CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior

“…It is also possible that different GC subtypes receive inhibitory inputs originating from distinct sources that confer different functions. A number of local and long-ranging GC-inhibitory inputs have been identified [1,50,51], but it is not known whether they segregate differently onto distinct GC subtypes. Altogether, our results provide evidence for the existence of functionally distinct GC subtypes in the adult OB and show that they each have a distinct involvement in odor behavior.…”