Biology subjects

Oldani, S.

Publications and source records attributed to Oldani, S..

3 recordsLinked to original sources

bioRxiv2025

Hippocampal Commissural Circuitry Shows Asymmetric cAMP-Dependent Synaptic Plasticity

Hemispheric asymmetries in NMDAR-dependent synaptic plasticity have been described in hippocampal area CA1, but it remains unclear whether similar lateralized mechanisms exist for cyclic adenosine monophosphate (cAMP)-dependent plasticity. Here, we investigated whether cAMP-mediated potentiation of synaptic transmission in mouse CA1 exhibits hemisphere-specific properties. In recordings with electrical stimulation of CA1 inputs, a subset of recordings in the left, but not in the right hemisphere CA1, exhibited a pronounced cAMP-induced potentiation of field excitatory postsynaptic potentials (fEPSPs). To isolate input specific contributions, we expressed the optogenetic actuator ChrimsonR unilaterally in the CA3/CA2 region of wild-type mice. Light-evoked glutamate release from ipsilateral Schaffer collaterals showed no cAMP sensitivity in either hemisphere, while commissures originating from the right (COR) exhibited cAMP-mediated potentiation of transmission in a subset of experiments. Notably, this effect was absent at commissures originating from the left (COL). The selective presence of the effect prompted us to further investigate the underlying cell population using CA3-specific (G32-4 Cre) and CA2-specific (Amigo2-Cre) driver lines. Recordings from synapses of CA3 COR recapitulated the cAMP-induced potentiation of transmitter release observed in wild-type animals. However, the effect was again restricted to a subset of experiments and was absent in recordings with specific stimulation of CA2 COR. Our results demonstrate a variable cAMP-sensitivity of transmitter release at COR synapses in the left CA1. Altogether, we reveal a hemisphere-specific cAMP-mediated synaptic plasticity at CA3 COR onto CA1, underscoring hidden heterogeneity and lateralization in hippocampal circuit function.

neuroscience↗

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↗

bioRxiv2020

Propagation of Hippocampal Ripples to the Neocortex by Way of a Subiculum-Retrosplenial Pathway

Bouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampo-cortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2-expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs.

neuroscience↗