Moreno-Velasquez, L. | bioRxiv Science

bioRxiv2020

SynaptoPAC, an Optogenetic Tool for Induction of Presynaptic Plasticity

Optogenetic manipulations have transformed neuroscience in recent years. While sophisticated tools now exist for controlling the firing patterns of neurons, it remains challenging to optogenetically define the plasticity state of individual synapses. A variety of synapses in the mammalian brain express presynaptic long-term potentiation (LTP) upon elevation of presynaptic cyclic adenosine monophosphate (cAMP), but the molecular expression mechanisms as well as the impact of presynaptic LTP on network activity and behavior are not fully understood. In order to establish optogenetic control of presynaptic cAMP levels and thereby presynaptic potentiation, we developed synaptoPAC, a presynaptically targeted version of the photoactivated adenylyl cyclase bPAC. In cultures of hippocampal granule cells, activation of synaptoPAC with blue light increases action potential-evoked transmission, an effect not seen in hippocampal cultures of non-granule cells. In acute brain slices, synaptoPAC activation immediately triggers a strong presynaptic potentiation at mossy fiber terminals in CA3, but not at Schaffer collateral synapse in CA1. Following light-triggered potentiation, mossy fiber transmission decreases within 20 minutes, but remains enhanced still after 30 min. Optogenetic potentiation alters the short-term plasticity dynamics of release, reminiscent of presynaptic LTP. SynaptoPAC is the first optogenetic tool that allows acute light-controlled potentiation of transmitter release at specific synapses of the brain, and will enable to investigate the role of presynaptic potentiation in network function and the animals behavior in an unprecedented manner. Significance StatementSynaptoPAC is a novel optogenetic tool that allows increasing synaptic transmission by light-controlled induction of presynaptic plasticity.

neuroscience↗

bioRxiv2019

Circuit-specific dendritic development in the piriform cortex

Dendritic geometry is largely determined during postnatal development and has a substantial impact on neural function. In sensory processing, postnatal development of the dendritic tree is affected by two dominant circuit motifs, ascending sensory feedforward inputs and descending and local recurrent connections. In the three-layered anterior piriform cortex, neurons in the sublayers 2a and 2b display vertical segregation of these two circuit motifs. Here, we combined electrophysiology, detailed morphometry and Ca2+ imaging in acute mouse brain slices and modeling to study circuit specific aspects of dendritic development. We observed that determination of branching complexity, dendritic length increases and pruning occurred in distinct developmental phases. Layer 2a and layer 2b neurons displayed developmental phase specific differences between their apical and basal dendritic trees related to differences in circuit incorporation. We further identified functional candidate mechanisms for circuit-specific differences in postnatal dendritic growth in sublayers 2a and 2b at the meso- and microscale level. Already in the first postnatal week, functional connectivity of layer 2a and layer 2b neurons during early spontaneous network activity scales with differences in basal dendritic growth. During the early critical period of sensory plasticity in the piriform cortex, our data is consistent with a model that proposes a role for dendritic NMDA-spikes in selecting branches for survival during developmental pruning in apical dendrites. The different stages of the morphological and functional developmental pattern differences between layer 2a and layer 2b neurons demonstrate the complex interplay between dendritic development and circuit specificity. Significance StatementSensory cortices are composed of ascending sensory circuits that relay sensory information from the periphery and recurrent intracortical circuits. Dendritic trees of neurons are shaped during development and determine which circuits contribute to the neuronal input space. To date, circuit-specific aspects of dendritic development and the underlying mechanisms are poorly understood. Here, we investigate dendritic development in layer 2 of the piriform cortex, a three-layered palaeocortex that displays a clear vertical segregation of sensory and recurrent circuits. Our results suggest that dendritic development occurs in distinct developmental phases with different circuit-specific properties. We further identify candidate mechanisms for neuronal activity patterns that could determine differences in circuit-specific dendritic development.

neuroscience↗