What’s the science?
Neurons communicate by receiving signals from the terminals (boutons) of other neurons via their dendritic arbour (many branch-like processes/dendrites). Each connection between a bouton and a dendrite is a ‘synapse’. How do postsynaptic neurons differentiate between input from different presynaptic neurons? Most research on this topic has focused on postsynaptic neurons; it has been found that the size and strength of postsynaptic dendrites depend on the distance away from the soma or cell body of the neuron. Presynaptic inputs could also differ by location along the dendritic arbour. This week in Neuron, Grillo and colleagues explored whether the structure and function of presynaptic inputs to dendrites of CA1 pyramidal neurons of the hippocampus varied with distance from the soma of the postsynaptic neuron.
How did they do it?
The authors performed electron microscopy on the hippocampus of an adolescent mouse brain (postnatal day 22) at three locations (proximal – close to pyramidal cell layer with cell bodies, middle, and distal) to assess the structure of neuron bouton/terminal (presynaptic) and dendrite (postsynaptic) structure. They then used a patch-clamping technique to visualize CA1 pyramidal cells with fluorescent dye in order to understand which inputs to the neurons resulted in short term facilitation: Stimulating pipettes were placed in proximal and distal regions outside of the pyramidal cells to stimulate boutons on presynaptic neurons in those regions, and resulting AMPA currents (i.e. important for synaptic plasticity) were measured. The authors also administered paired electrical pulses to assess response of the postsynaptic neurons to multiple inputs. They then blocked NMDA receptor (neurotransmitter receptor) release (using a blocker; MK-801) to observe changes in neurotransmitter release (indicating neurotransmitter release potential). Finally, the authors created a computational model that mimicked the short-term potentiation/facilitation gradient they found between proximal and distal synapses.
What did they find?
They found that in proximal layers (closer to the soma), dendrite spines were larger. This is expected because dendrite size usually varies by distance from the soma. Critically, size of dendrite spine was related to the size of bouton active zones. Active zones themselves were also larger in proximal layers. These findings suggest that the structure of presynaptic neuron terminals (boutons) varied by distance from the pyramidal cell layer (somas of hippocampal neurons). When the authors used a fluorescent dye to assess AMPA (neurotransmitter) currents after stimulation, they found that excitation was greater for distal inputs (there were larger larger excitatory postsynaptic potentials). When paired pulses were administered at distal locations (versus proximal), neurons were more likely to exhibit larger responses to the second pulse in a supra-linear manner. However, when an NMDA receptor blocker was applied, decay in current was faster at proximal synapses, indicating more neurotransmitter release initially. Therefore, the results suggest that short-term potentiation was greater at distal synapses, but release probability was greater at proximal synapses. In a computational model, when distal synapses with greater short-term potentiation were stimulated, a larger response was generated. The authors suggest that greater short-term potentiation distally may counteract passive decay of a signal along a dendrite.
What’s the impact?
This study is the first to show that structure and function of presynaptic boutons varies along a gradient in a distance-dependent manner; at more distal synapses, dendritic spines are smaller and have a lower release probability, but short-term excitation is greater, possibly as compensation for signal attenuation. This work has important implications for understanding how neurons integrate information from different locations.
Grillo et al., A Distance-Dependent Distribution of Presynaptic Boutons Tunes Frequency-Dependent Dendritic Integration. Neuron (2018). Access the original scientific publication here.