Is the hippocampal mossy fiber synapse a detonator in vivo?

Información del proyecto

IN VIVO MOSSY

Identificador del acuerdo de subvención: 709328

DOI

10.3030/709328

Proyecto cerrado

Fecha de la firma de la CE 16 Marzo 2016

Fecha de inicio 1 Abril 2016

Fecha de finalización 31 Marzo 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 166 156,80

Aportación de la UE

€ 166 156,80

Coordinado por

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Austria

Periodic Reporting for period 1 - IN VIVO MOSSY (Is the hippocampal mossy fiber synapse a detonator in vivo?)

Período documentado: 2016-04-01 hasta 2018-03-31

Resumen del contexto y de los objetivos generales del proyecto

A commonly repeated maxim is that an individual cortical neuron receives synaptic input from tens of thousands of presynaptic partners, with each individual connection carrying only minor weight. In that case, concerted firing by many presynaptic neurons is required to cause an action potential in the postsynaptic neuron. However, there is circumstantial evidence that the mossy fiber synapse (the second connection in Cajal’s heavily studied “trisynaptic circuit” of the hippocampus) is powerful enough to translate a single presynaptic spike into a postsynaptic spike - termed “detonation”. If true, this would have substantial implications for our understanding of learning and memory, spatial navigation, and pattern recognition. Thus, the results will likely be of general interest.
The overall objective is to image the activity of CA3 pyramidal neurons in awake mice navigating along a linear track, and also to image activity in presynaptic mossy fiber terminals. Together this may conclusively confirm or rule out the detonation hypothesis. This approach allows to distinguish between detonator, conditional detonator, and subdetonator synapses, and more generally to quantify the number of simultaneously active mossy fiber boutons necessary to cause CA3 spiking during behavior. Such results would have substantial implications for established models of associative memory and spatial navigation, and more generally for information transfer in the hippocampus.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

For this study, the region of interest – CA3 – lies deep within the hippocampus, making it difficult to obtain images from neurons at this location and to measure calcium transients at high resolution. Thus, the majority of our work has focused on improving on existing state-of-the-art techniques, in order to obtain suitable images. We adopted an iterative process, and considered all aspects of the experimental system, including the microscope, the imaging implant, techniques for expressing fluorescent indicators in the brain, and post-processing software routines.
These efforts have produced dividends: we have succeeded in obtaining high-quality images from the CA3 region in awake, behaving mice, and are using this approach to quantify the population activity of CA3 pyramidal neurons during spatial navigation. These results have been accepted for presentation at a large conference.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

How the brain works is a question of great general interest to the public, both to satisfy innate curiosity and in hope that even partial answers may ameliorate human suffering in disease. By the end of this study, the expected results have the potential to shed light, at multiple levels, on fundamental mechanisms of memory and synaptic transmission. The targeted brain circuits are not only instrumental in the healthy brain, but also implicated in a broad range of brain disorders. Our technical advances have been developed in a small mammalian model system, but may one day contribute to therapeutic interventions.