Biomedical
Synaptic plasticity through a naturalistic lens
Peer Reviewed
Abstract
From the myriad of studies on neuronal plasticity, investigating its underlying molecular mechanisms up to its behavioral relevance, a very complex landscape has emerged. Recent efforts have been achieved toward more naturalistic investigations as an attempt to better capture the synaptic plasticity underpinning of learning and memory, which has been fostered by the development of in vivo electrophysiological and imaging tools. In this review, we examine these naturalistic investigations, by devoting a first part to synaptic plasticity rules issued from naturalistic in vivo-like activity patterns. We next give an overview of the novel tools, which enable an increased spatio-temporal specificity for detecting and manipulating plasticity expressed at individual spines up to neuronal circuit level during behavior. Finally, we put particular emphasis on works considering brain-body communication loops and macroscale contributors to synaptic plasticity, such as body internal states and brain energy metabolism.
Why is studying synaptic plasticity with naturalistic approaches important?
Naturalistic approaches are important because:- They better capture synaptic plasticity underpinning learning and memory
- They provide insight into how in vivo neuronal activity causes synaptic plasticity
- They help understand the specific functions and interplay of diverse plasticity rules during learning
- They enable the identification of molecular determinants that could be used for manipulating plasticity expression in vivo
What are some key naturalistic plasticity induction protocols?
Key naturalistic plasticity induction protocols include:- Theta-burst stimulations based on in vivo recordings of place cells
- Spike-timing dependent plasticity (STDP) paradigms using low-frequency firing patterns
- STDP with smaller numbers of pairings (5-30) to mimic single-trial or one-shot learning
- Complex spiking sequences such as spike triplets or quadruplets
- In vivo spiking patterns replayed between neighboring neurons in vitro
- Associating natural sensory stimulation with evoked or spontaneous spiking of cortical neurons in vivo
What are some challenges in translating STDP to in vivo conditions?
Challenges in translating STDP to in vivo conditions include:- Determining the exact contribution of spike timing relative to firing rate in eliciting synaptic plasticity
- Addressing whether plasticity can only be induced by a global feedback signal like backpropagating action potentials
- Reconciling the compressed timescale of STDP with behavioral timescales
- Understanding the role of digital (action potentials) versus analog (EPSPs) signals in inducing plasticity in vivo
How have researchers addressed these challenges?
Researchers have addressed these challenges by:- Studying input-timing-dependent plasticity (ITDP), which relies on temporal correlation between distinct presynaptic afferents
- Investigating nonlinear slow-timescale mechanisms and three-factor learning rules incorporating neuromodulators
- Discovering behavioral timescale plasticity (BTSP) that operates on longer timescales without requiring precise spike timing
- Examining heterosynaptic plasticity mechanisms and interactions between inhibitory and excitatory neurons
