Cells proliferate in the entire central nervous system, but only in the hippocampus and the olfactory bulb do they generate neurons. However, when proliferative cells of non-neurogenic areas are transplanted into the hippocampus, they generate neurons. Thus, the neurogenic potential of stem cells depends on their environment.

So the question is:

“What is so special about the stem cell environment in the hippocampus?“

We are addressing this question from two ends:

1. An innocent view:

What is the cellular environment of hippocampal neural stem cells?

Using novel microscopy and identification approaches, we are examining stem cells and their close environment in detail. We recently found that these cells establish very close contacts with blood vessels, astrocytes and neurons; observations that are consistent with previous work showing that adult neurogenesis is regulated by circulating blood factors or neuronal activity.

Using remote control of cellular activity we are investigating the role of these different cell types in the regulation of stem cell activity, with the hope of deciphering the neurogenic code of the hippocampus.

For more, read our recent article in PNAS 2016: Moss et al.

RGL model

Radial glia-like stem cell (blue) interacts with neurons (green), blood vessels (red) and astrocytes (yellow). (4): Some processes in the molecular layer make small endfeet-like contacts onto blood vessels. Astrocytic processes share the blood vessel surface with the processes of the stem cell, with adhesion points where they meet. (5,6): Finer processes extend from these varicosities to approach and/or wrap around local asymmetrical synapses (light red).

2. A committed view:

Do astrocytes regulate adult hippocampal neurogenesis?

Astrocytes secrete a range of molecules that play crucial roles in neuronal function. So we started investigating whether they regulate neurogenesis.

By blocking vesicular release of astrocytes, we found that they play a role in the survival and maturation of the new neurons. We identified that D-serine is required for the synaptic integration of new neurons in the mature neuronal network (Sultan et al. Neuron 2015). Interestingly, D-serine is currently tested in Human for its effects on cognition and anxiety, part of which may be mediated by adult neurogenesis. See the video highlight here .

We are now identifying other molecules released by astrocytes that regulate different stages of adult neurogenesis with the hope of improving memory performance or alleviating depression-related symptoms.

01_Nicolas-_Toni_Brain Crowd_03

Composite image of the adult hippocampus showing neural stem cells (green) astrocytes (blue), neurons (red) microglia (white) and blood vessels (yellow).