CNS*2025 Florence

Adult Neurogenesis Reconciles Flexibility and Stability of Olfactory Perceptual Memory

Bennet Sakelaris, Hermann Riecke


Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL, 60208, USA



h-riecke@northwestern.edu



Introduction
The brain must balance two competing demands: flexibly forming new memories while maintaining stability of old ones. This is known as the flexibility-stability dilemma. When memories are tagged by salient cues like reward or punishment, neuromodulatory signals can protect them from being overwritten. In their absence, however, this balance is harder to maintain. The rodent olfactory bulb (OB) offers a compelling model for studying this problem, as the OB is known experimentally to support perceptual learning from neutral sensory experience through adult neurogenesis [1,2]. Here we show using a computational model how the dynamically changing intrinsic properties of developing newborn neurons resolve the flexibility-stability dilemma [3].


Methods
We develop an anatomically constrained firing rate model of the OB composed of two populations of neurons: excitatory mitral cells (MCs) and inhibitory granule cells (GCs), the primary neurogenic population. The network, with characteristic reciprocal MC-GC synapses, learns a fine odor discrimination task via an unsupervised activity-dependent synaptic plasticity rule. Neurogenesis is implemented by continually adding a biologically plausible number of adult-born GCs (abGCs) to the network, and newborn neurons feature transiently elevated intrinsic excitability and plasticity rates (Fig. 1). An age- and activity-dependent apoptosis rule captures the high turnover of adult-born neurons.

Results
The model shows explicitly how neurogenesis, apoptosis, the transiently enhanced excitability, and structural plasticity, combine to enable the flexible formation of stable odor memories. The model demonstrates that all three components, neurogenesis, apoptosis, and transient properties of abGCs, are necessary to achieve this goal. Moreover, in line with experiments, we show how memories are encoded by young abGCs, how these memories are briefly vulnerable to interference from a new stimulus, how re-learning a lost memory is faster than learning a new memory, and how the OB can learn several odors at the same time. The model predicts that odor exposure leads to the formation of birthdate-dependent, odor-specific subnetworks in the OB.

Discussion
While experiments show adult neurogenesis is required for perceptual learning, in principle this can be done using synaptic plasticity alone. What then is the precise role of adult neurogenesis? We show that the strong impact of neurogenesis arises from the transiently different intrinsic properties of young neurons. The evolution of these properties provides a vast gain in memory duration: it boosts memory duration from log(N) in a network of non-aging neurons with N synapses to sqrt(N) for aging neurons, an expansion commensurate with other theoretical models designed to solve the flexibility-stability dilemma. This work shows how the aging of neurons can enhance the stability and flexibility of memories beyond olfaction.





This work was supported by the NSF (DMS-1547394) and NIH (DC015137). B.S. was supported by a John N. Nicholson fellowship.

[1] Moreno, M. M.; Linster, C.; ...; Mandairon, N.
Olfactory perceptual learning requires adult neurogenesis.
Proc Natl Acad Sci U S A, 2009, 106, 17980. https://doi.org/10.1073/pnas.0907063106
[2] Forest, J.; Moreno, M.; Mandairon, N. Short-term availability of adult-born neurons for memory encoding.
Nature communications, 2019, 10, 5609. https://doi.org/10.1038/s41467-019-13521-7
[3] Sakelaris, B. & Riecke, H.
Adult Neurogenesis Reconciles Flexibility and Stability of Olfactory Perceptual Memory.
eLife (to appear). https://doi.org/10.7554/eLife.104443