Nabavi Group


Nabavi group - Memory formation and consolidation at the synaptic and circuit levels

 


The Nabavi group is focusing on how plasticity at the synaptic and circuit levels in the brain relates to behavioral plasticity (learning and memory formation) and how the newly formed memories are integrated into the existing network (cellular and systems consolidation) using rodents as model organism.

Research focus

The idea that changes in synaptic strength (synaptic plasticity) is the foundation of memory and learning has a long history. For this reason long term potentiation (LTP) and long term depression (LTD), the electrophysiological manifestations of synaptic plasticity, have been intensely studied. However, the proof of causality, that by changing synaptic strength one can remove and reinstate a memory, had been missing.

In our recent paper we provided the most direct evidence showing a cause-effect relation between synaptic plasticity and memory formation (Nabavi et al., 2014, Nature). With the use of optogenetics fortified by in vitro/in vivo recording and behavioral assays we generated an associative memory and showed that we could repeatedly turn off and on this associative memory simply by inducing LTD and LTP (see the figure).

An immediate question following this study is how these newly formed memories are integrated into the existing network. This is a vital concern for any system that aims to store and retrieve information. Our brain is continuously exposed to external sensory inputs. This amount of information can overwhelm any storage device no matter how large its capacity. Therefore, a challenge for our brain is to decide which information is worthy of permanent storage. The storage process itself, however, poses another challenge: how to integrate new information into a network of pre-existing memories without “catastrophic interference” (forgetting).

The first challenge is commonly known as synaptic consolidation, which takes place within the first minutes to hours after memory formation. The second challenge, known as systems consolidation, is a slower process that takes weeks, months or even years. The major focus of my research is to understand how our brain tackles these challenges. To this end we will use a combination of tools such as molecular biology, in vitro and in vivo electrophysiology, two-photon laser scanning microscopy, optogenetics, behavioral analysis (i.e. whatever it takes) to move forward.

These studies may lead us to better understand and treat better neuropsychological diseases thought to be related to aberrations in synaptic plasticity, such as posttraumatic stress disorder, schizophrenia, substance abuse disorders and dementia.

a) Fear conditioning with optogenetics. Diagram of rat’s fear memory circuit receiving optogenetically driven input stimulation (laser) paired with a shock (left). Animal is tested one day later (right) by optical activation of the input (blue). Time plot shows normalized number of lever presses (1 min bins) to a previously learned cued lever-press task. b) LTD inactivates memory. In vivo field response in lateral amygdala to single optical stimulus (left) before and after LTD induction (1Hz). Animal is tested one day later (right). c) LTP reactivates memory. Same as b) except animal receives an LTP protocol (100Hz).

News

2017.07.04 | Research news

Sadegh Nabavi, Niels Andersen and Nathalie Krauth publish a review article in Current Opinion in Neurobiology

The title of the review is: Hebbian plasticity in vivo: relevance and induction.

2017.05.17 | Research news

Marco Capogna and Sadegh Nabavi publish a paper in the prestigious journal Neuron edited by Cell Press, 17 May 2017

The title of the paper is: “Synaptic plasticity and network oscillations in amygdala circuits for storage and retrieval of emotional memories”.

2017.05.05 | Awards

DANDRITE researchers receive DFF-Research Project Grants from the Danish Council for Independent Research

Core group leaders Anders Nykjær and Poul Nissen, group leader Sadegh Nabavi and team leader Magnus Kjærgaard are all recipients of research grants from the FNU, FSS and FTP sections of DFF.

2016.12.16 | Awards

Novo Nordisk Foundation grant to Sadegh Nabavi

Sadegh Nabavi has received a grant of DKK 700.000 from the Novo Nordisk Foundation. The grant is to support the project "Mapping the Neural Circuit for an Innate Fear Behavior".

2016.11.24 | Research news

Sadegh Nabavi granted 2 million DKK by AUFF NOVA to study fear

Sadegh Nabavi will receive the grant over a 3 year period for a project dedicated to map the brain circuit for an innate fear. The innate fear studied is in rodents for predator. Ultimately, the goal is to know what's the difference between a learned fear and innate fear at the circuit and synaptic levels.

2016.09.26 | People

Group Leader Sadegh Nabavi appointed AIAS Associate

AIAS will give its official welcome to three new AIAS Associates on 3 October 2016. One of them is Sadegh Nabavi, Group Leader at DANDRITE. The ‘AIAS Associates’ has been established as a means to provide Aarhus University internationals at a high-level with a formal access and link to the international environment at AIAS.

Sadegh Nabavi has been awarded one of the prestigious ERC Starting Grants. (Photo: DANDRITE)
Figure 1. Sadegh Nabavi will use optogenetics to modify memory strength at the synaptic level to study why only some synapses, and hence memories, become permanent (Figure: Sadegh Nabavi)
Figure 2. a) Fear conditioning with optogenetics. Diagram of rat’s fear memory circuit receiving optogenetically driven input stimulation (laser) paired with a shock (left). Animal is tested one day later (right) by optical activation of the input (blue). Time plot shows normalized number of lever presses (1 min bins) to a previously learned cued lever-press task. b) LTD inactivates memory. In vivo field response in lateral amygdala to single optical stimulus (left) before and after LTD induction (1Hz). Animal is tested one day later (right). c) LTP reactivates memory. Same as b) except animal receives an LTP protocol (100Hz). (Figure: Sadegh Nabavi, published in Nature (Nabavi et al., 2014))

2015.11.19 | Awards

ERC Starting Grant for research in memory formation and consolidation

DANDRITE Group Leader Sadegh Nabavi is awarded an ERC Starting Grant of EUR 1.5 million for research into memory formation to answer the fundamental questions on why some memories last and some are soon lost.

(Copyright: Colourbox)
Sadegh Nabavi (Photo: private)
Mark Denham (Photo: private)
Anne von Philipsborn (Photo: DANDRITE)
Duda Kvitsiani (Photo: DANDRITE)
Keisuke Yonehara (Photo: DANDRITE)

2015.05.29 | People

Top team of Group leaders now complete at DANDRITE

DANDRITE’s aim of appointing five top researchers as Group leaders has just become a reality with the appointment of Dr Sadegh Nabavi, whose research includes how memory is formed, how it can be erased, and how it can subsequently be restored.

2015.05.22 | People

New Group Leader appointed at DANDRITE

Sadegh Nabavi has been appointed as the fifth Group Leader at DANDRITE, thus completing the new group leader recruitments at DANDRITE. Sadegh Nabavi will start his research activities on memory formation and consolidation at the synaptic and circuit levels in the summer 2015. Sadegh Nabavi’s research focus is on understanding how plasticity at the…