Ongoing interplay between the neural network and neurogenesis in the adult hippocampus

Abstract

As a unique form of structural plasticity in the central nervous system, adult neurogenesis in the hippocampus alters network functions by continuously adding new neurons to the mature network, while at the same time is subjected to regulation by surrounding network activity. Here, we review the recently identified mechanisms through which network activity exerts its impacts on multiple steps of adult neurogenesis in rodents and culminates in the selective recruitment of new neurons. We also review recent progress on the study of cellular connectivity modified by new neurons in the dentate gyrus and its physiological functions in rodents. We believe that understanding these processes will allow eventual elucidation of the mechanisms controlling the development of balanced inputs and outputs for the adult-born neurons and reveal important insights into the cellular organization of learning and memory.

Figure 1. Interplay between the neighboring network and ongoing neurogenesis in the dentate gyrus

Neurogenesis in the dentate gyrus involves progressive sequences involving progenitor proliferation, neuron production, neuronal maturation and integration. The activities of the neighboring network can influence ongoing neurogenesis via growth/trophic factors or neurotransmittors. On the other hand, persistent neurogenesis constantly shapes the network by adding new granule neurons.

Figure 2. The effects of task-specific inputs on neurogenesis

In response to task-specific inputs, progenitor proliferation, cell survival and neuronal differentiation can occur either globally (A) or specifically in the neurogenic regions adjacent to the inputs (B). Yellow cells represent the existing granule cells and green cells represent the new granule cells produced as a result of progenitor proliferation, cell survival and neuronal differentiation. GCL, granule cell layer.

Figure 3. Basic connections of the granule cells of the dentate gyrus

(A) Mature granule cells (GCs) send outputs to: CA3 pyramidal cells (PCs, a), hilar mossy cells (MCs, b), and interneurons (INs, c and d). MCs can activate GCs located (e) or INs (f). INs can further mediate feedforward inhibition on CA3 PCs (g) or feedback inhibition on GCs (h or i). Mature GCs receive inputs from entorhinal cortex (EC) and local neurons including MCs (e) and INs (h or i). (B) Adult-born GCs receive inputs from EC, INs and possibly MCs. In the meantime, they send axons to targets including CA3 PCs, MCs and INs. The “vee” arrows stand for stimulation and “box” arrows for inhibition. Dashed line is the unconfirmed connection. GCL, granule cell layer.

Figure 4. Cellular connections altered by addition of adult-born GCs in the DG

(A and B) Adult-born granule cells (GC) can preferentially encode new inputs by making connections to naïve CA3 pyramidal cells (PC) (A), or by making connections to the CA3 PCs activated by the experienced input (B), thus experienced and new inputs can be associated at the CA3 level. (C and D) The experienced inputs can also activate adult-born GCs that make new connections to CA3 PCs (C). When two different inputs are present close in time, the adult-born GC can associate both and make overlapping projection to the CA3 field (D). (E and F) Upon stimulation, the adult-born GCs can inhibit other GCs through hilar interneurons (INs) (E) or suppress CA3 PCs through INs in the strata pyramidale and lucidum of the CA3 area (F). (G and H) The adult-born GCs can stimulate the hilar mossy cells (MCs), which can either activate GCs at other levels (G) or inhibit other GCs via INs (H). GC, granule cell; GCL, granule cell layer; PC, pyramidal cell; IN, interneuron; MC, mossy cell.