Optical controlling reveals time-dependent roles for adult-born

dentate granule cellsYan Gu, Maithe Arruda-Carvalho, Jia Wang, Stephen

R Janoschka, Sheena A Josselyn，Paul W Frankland & Shaoyu Ge

1

Background

The adult hippocampus continues to give rise to several thousand new dentate granule cells everyday.

Studies using global perturbation or ablation of adult hippocampal neurogenesis has revealed deficits in some forms of hippocampal memory.

.

2

As the morphological and physiological phenotypes of adult-born cells change markedly as they mature, they may have distinct roles at different stages following integration into hippocampal circuits.

Adult-born dentate granule cells (DGCs) extend dendrites receive functional input from the existing neural circuits as early as 2 weeks after birth.

Input (dendritic) synapses of adult-born neurons show enhanced plasticity between 4–6 weeks after birth compared with other stages.

Background

3

What is the precise timing for these adult-born functional output synapse formation and maturation?

Whether do output synapses, if formed and functional, also exhibit heightened plasticity around the same time?

What is its functional role?

Questions

4

Methods

Optogenetic stimulation

Water mazeClassical fear conditioning

Retroviral birth-dating + Gene delivery(EGFP+ Light gated ion channels)

Electrophysiological experiments

Behavioral experiments

Synaptic transmission efficiency, Capability of LTP

5

Results

Birth-dating and labeling newborn DGCs

Experimental timeline

Labeling specificity of newborn DGCs with high-titer retrovirusNo mature DGC-like cells at 1 and 2 wpi

6

Results

Adult-born DGCs fully integrate into the hippocampal trisynaptic circuits by ~4 wpi

Adult-born neurons form functional synapses on CA3 pyramidal neurons

7

Results

Heightened synaptic plasticity of young adult-born neurons

8

Results

Output synapses of mature newborn DGCs remain plastic, but have a higher induction threshold

Young newborn neurons exhibit heightened plasticity that peaks at ~4 wpi9

Conclusion 1

• Adult-born DGCs fully incorporate into the hippocampal trisynaptic neural circuit around 4 wpi and DGCs at this age have more excitable membranes and enhanced input/output synaptic plasticity.

10

ResultsOptical silencing of newborn DGCs does not

influence acquisition of spatial memory

11

ResultsSilencing young newborn neurons affects

spatial memory retrieval

labeled ~4-week-old adult-born DGCs regulate spatial memory retrieval. 12

ResultsSilencing young newborn neurons impairs

retrival of contextural fear memory

13

ResultsThe behavioral role for newborn DGCs relies on their age

14

Results

Heightened plasticity in young newborn neurons may be important for memory retrieval

15

Results

Silencing newborn neurons at 4 wpi, but not 8 wpi, disrupted memory retrieval in both tasks

16

Conclusion 2

• Adult-born neurons may be transiently critical for memory retrieval, but the effect, at least in spatial and contextual memory retrieval, may decline as these adult-born neurons continue to mature.

17

Thank you

18