3D functional network and dendritic imaging

Group 15
Leader: Balázs Rózsa


To better understand the computational mechanism of the brain we need complex techniques to be able to measure from a large population of neurons, but also with great details and subcellular resolution. The main goal of our group is to adopt and develop novel imaging techniques accompanied with advanced software and hardware technologies for scientific research which make this quest attainable. With our novel developments it became possible to follow the activity of the entire dendritic tree of a neuron in three dimensions or to record hundreds of cells simultaneously in an intact neuronal network (Katona et al. 2011 PNAS, Katona et al. 2012 Nature Methods, Szalay et al. 2016). Having these techniques in hand, we turn to various biological questions that could only be addressed with these novel tools.

  • First, our research group examines the elementary units of memory and its function in vitro and in vivo. Hippocampal sharp wave-ripple (SPW-R) complexes have a crucial role in memory formation and consolidation. Our main aim is to understand how the brain encode the information acquired during learning in its dendrites, cells, and networks. To manage the experiments, high-precision two-photon microscopic procedures (imaging and photostimulation) as well as electrophysiological (single or multichannel) and pharmacological measurements are performed in vitro and in vivo. Our technical equipments make it possible to measure local field potentials simultaneously with large neuronal populations (pyramidal cells and interneurons) and their dendritic activity during SPW-R. Our results highlight the importance of dendritic signal integration during hippocampal rhythms. To validate and modulate the physiological data we use two-photon uncaging techniques, which allow us to release either excitatory or even inhibitory neurotransmitters from our own cage compounds with high precision, locally and repeatably.
  • In another project, we aim to reveal the background mechanisms of interictal events characteristic of epilepsy. These events may have a key role in the decline of memory and navigation capabilities described in patients. In our experiments, we investigate the activity of cortical networks in vivo in the chronic phase of epilepsy with cell-type-specific two-photon imaging as well as with depth and surface electrodes. Describing the dynamics of interictal events may contribute to a better understanding of epilepsy.
  • In another research topic we investigate in awake mice with 2 photon microscopy, how the activity of neocortical pyramidal dendrites and distinct interneuron subtypes are related. We monitor the representation of reinforcement signals and effects of neuromodulatory (cholinergic and serotonergic) inputs, while mice are performing auditory and visual discrimination tasks. The three-dimensional acousto-optical imaging enables us to measure the activity of sparse interneuron populations, like VIP interneurons, which make up 1% of the cortical cells. Our results highlight how the reinforcers affect the sensory processing on the level of microcircuits and give new insights to the cellular network level mechanisms of associative learning.
  • Earlier doctrine regarded primary sensory cortices as simple pattern recognition areas. Contrary to this, functional measurements from behaving mice revealed that responses to a given stimuli show great trial to trial variability and numerous factors affect their cortical representation. We are studying the effect of learning-related plasticity and investigate the changes in the cortical representation of distinct visual stimuli during learning. Besides, we use optical stimulation to investigate the local dendritic integration, simultaneously on multiple dendritic segments, to better understand the formation of the specific output signals.
  • These research projects require unique cell-marking techniques. Monitoring the activity of cells and cellular parts by two photon microscopy, and also the modulation of their activity by light happens by using genetically encoded toolset. Transferring these tools into the cells may be attained effectively and in a secure way by adeno-associated viral vectors (AAVs). Therefore our group founded a unit specialized for creating these viral agents. The lab consist of a molecular biology and a tissue-culture division which have the duty of providing the research teams with custom designed viral vectors. Our long-term goals include the creation of cell-line specific tools for human genetic therapy.

Excerpt from the Guidebook of the Institute 2015.

Grant:

  • ERC Consolidator Grant (682426, VISIONby3DSTIM)

Group webpage: rozsalab.eu

Lab members:

NamePosition
Balázs RózsaGroup Leader, Senior Research Fellow
Gergely KatonaVisiting Scientist
Gergely SzalayResearch Fellow
Áron SzepesiResearch Fellow
Balázs ChioviniResearch Fellow
Plauska AndriusResearch Fellow
Dénes PálfiVisiting Scientist
Linda JudákVisiting Scientist
Tamás TompaVisiting Scientist
Gábor JuhászVisiting Scientist
Éva JámborTechnician
Lászlóné BátkaiTechnician
Alexandra BojdánTechnician
Zoltán SzadaiPhD Student
Miklós MadarászPhD Student
Domonkos PinkePhD Student
Dominika NagyPhD Student
Csaba CsupernyákUndergraduate Student