John J Tukker

John J Tukker
Deutsches Zentrum für Neurodegenerative Erkrankungen Berlin · RG Network Dysfunction

DPhil Neuroscience

About

19
Publications
13,408
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
849
Citations
Introduction
I am using in vivo electrophysiology and optogenetics to elucidate functional connectivity between specific cell types, in relation to behavior (navigation and memory) and brain states (oscillations). We are focussing on the hippocampal formation and connected structures in mice, including mouse models of Alzheimer's disease.
Additional affiliations
July 2018 - present
Deutsches Zentrum für Neurodegenerative Erkrankungen
Position
  • PostDoc Position
April 2015 - present
Charité Universitätsmedizin Berlin
Position
  • Lecturer
February 2014 - present
Charité Universitätsmedizin Berlin
Position
  • PostDoc Position
Education
October 2005 - November 2009
University of Oxford
Field of study
  • Neuroscience
September 2004 - August 2005
International Max Planck Research School
Field of study
  • Neuroscience
September 1996 - December 2001
Utrecht University
Field of study
  • Cognitive Artificial Intelligence

Publications

Publications (19)
Article
Full-text available
Cortical gamma oscillations contribute to cognitive processing and are thought to be supported by perisomatic-innervating GABAergic interneurons. We performed extracellular recordings of identified interneurons in the hippocampal CA1 area of anesthetized rats, revealing that the firing patterns of five distinct interneuron types are differentially...
Article
Full-text available
Hippocampal CA3 area generates temporally structured network activity such as sharp waves and gamma and theta oscillations. Parvalbumin-expressing basket cells, making GABAergic synapses onto cell bodies and proximal dendrites of pyramidal cells, control pyramidal cell activity and participate in network oscillations in slice preparations, but thei...
Chapter
Full-text available
A deeper understanding of the brain is likely to require detailed, quantitative descriptions at several levels, ranging from the molecular to the behavioral, as well as an understanding of the relations among these levels. Taking the single neuron as the basic building block, I will here outline recent progress in linking different levels of descri...
Article
Full-text available
Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer s...
Article
Full-text available
Unlabelled: The presubiculum provides a major input to the medial entorhinal cortex (MEC) and contains cells that encode for the animal's head direction (HD), as well as other cells likely to be important for navigation and memory, including grid cells. To understand the mechanisms underlying HD cell firing and its effects on other parts of the ci...
Article
The hippocampal formation is critically involved in learning and memory, and contains a large proportion of neurons encoding aspects of the organism's spatial surroundings. In the medial entorhinal cortex (MEC), this includes grid cells with their distinctive hexagonal firing fields, as well as a host of other functionally defined cell types includ...
Article
Full-text available
Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical ne...
Preprint
Full-text available
Serotonin (5-HT) affects multiple physiological processes in the brain and is involved in a number of psychiatric disorders. 5-HT axons reach all cortical areas; however, the precise mechanism by which 5-HT modulates cortical network activity is not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SO), a synchronized...
Article
Full-text available
In the course of a day, brain states fluctuate, from conscious awake information-acquiring states to sleep states, during which previously acquired information is further processed and stored as memories. One hypothesis is that memories are consolidated and stored during “offline” states such as sleep, a process thought to involve transfer of infor...
Article
Full-text available
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-corti...
Preprint
Full-text available
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-corti...
Article
Full-text available
In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports the required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in this differentiation process is unknown. Here, we demons...
Article
Full-text available
Unlabelled: The parasubiculum is a major input structure of layer 2 of medial entorhinal cortex, where most grid cells are found. Here we investigated parasubicular circuits of the rat by anatomical analysis combined with juxtacellular recording/labeling and tetrode recordings during spatial exploration. In tangential sections, the parasubiculum a...
Article
Full-text available
Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when...
Article
Full-text available
Virtually nothing is known about the activity of morphologically identified neurons in freely moving mammals. Here we describe stabilization and positioning techniques that allow juxtacellular recordings from labeled single neurons in awake, freely moving animals. This method involves the use of a friction-based device that allows stabilization of...
Article
Full-text available
Hippocampal oscillations reflect coordinated neuronal activity on many timescales. Distinct types of GABAergic interneuron participate in the coordination of pyramidal cells over different oscillatory cycle phases. In the CA3 area, which generates sharp waves and gamma oscillations, the contribution of identified GABAergic neurons remains to be def...
Article
Full-text available
The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in Onglobal” signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic t...

Questions

Questions (9)
Question
I was looking around for a new perfusion pump for mouse transcardial perfusion and fixation of the brain (and subsequent IHC), and came across this Perfusion Two system from Leica which not only seems very convenient (perfusion in seconds) but also claims to prevent shrinkage and be generally more reliable and effective (by using a particular (high) pressure rather than relying on a set flow rate). It would be great if anyone who is not from Leica could share their experiences with this system, compared to a 'standard' pump or even gravity perfusion system!
Question
Given the slow washout of CNO, it would be great if one could stop its effects on hM4Di with some drug (that ideally does not affect native M4 receptors).  Bryan Roth mentioned in his 2016 Neuron Primer "DREADDs for Neuroscientists" that 
"creation of DREADD antagonists would also be potentially highly useful", so apparently at that time there still was none. I would think it might be possible to create/discover something that eg blocks the CNO binding site, but so far found nothing! 
I only found a paper from 2008 that looked into this a bit but did not find any antagonists (https://www.ncbi.nlm.nih.gov/pubmed/18628403). If anyone knows of anything, would be great to hear about it!
Question
I intend to use the Callaway approach with (EnvA-deltaG) rabies virus for monosynaptic retrograde tracing. My idea is to inject, at the same time as the rabies, the 'classical' retrograde tracer Fast Blue, as a kind of positive control. Does anyone have experience with that?? I'm worried that Fast Blue might somehow disturb the action of the rabies virus..
Question
I mixed AAV9 and some borrowed AAV2 (both with EF1a, FLEX and ChR2, but with 2 different fluorophores) into an epi so that I can inject them together, to assess effect of serotype directly at the same injection site (in Cre mouse).
I made the epi one week ago and kept in the fridge ever since, unsure if there is any danger of some sort of interaction! More generally, can one simply mix the viruses like that and still assume them to be independent? Do they compete in the brain to infect the same cells? Would be great is someone could share their experience/insights/refs! Obviously one could jsut do two separate injections to avoid this issue, but it would be easier, faster, and make for a better comparison if I just combine into one injection.. cheers
Question
3 weeks appears to be the max in the studies I've read so far; found no studies beyond that, although I know people do wait longer. Also found no systematic evaluation. Would be great if someone could send me a reference! Many thanks in advance.
Question
In pfa-fixed 70um thick sections, I have neurobiotin-filled cells (spiny, pyramidal-like morphology), mostly in the presubiculum, for which I would like to confirm that they are glutamatergic pyramidal cells using fluorescence microscopy. Two complications:
1. for most cells, only the dendrites and soma are visible, so no axon (terminals).
2. Because of previous reactions done with these sections, I only have one channel left, so I can only use one antibody! (i.e. I cannot use an additional marker to prove that cells are not GABAergic or not glial cells)
Maybe it's just not possible to get a 100% answer, but I'd like to get as close as possible :). Any suggestions very welcome! Eg any opinions on Emx1? Thanks!
Question
If the frequency band is eg 4 to 12 Hz (theta), then three 12Hz cycles fit within one 4Hz cycle, so does it still make sense to compute one phase for an action potential?? How can one say that a cell "fires on the trough" of a certain freq band if one defines the band so widely? As a non-mathematician, looking at the results of a Hilbert transform (with Matlab) it seems like the lower (higher power?) frequencies dominate in terms of deciding the phase.
Intuitively, I'd say one should take narrower bands if possible (possibly in a dynamic way, since the peak frequency can change over time), OR make very sure that the actual frequency peak is narrow (but what is 'narrow'?). I'd welcome any thoughts on this!
Question
AD patients tend to wander and get lost/disoriented. I'm not sure if the standard Morris Water Maze is necessarily the best task to test AD mouse models on, in relation to this question. I'm interested in testing a possible role for head-direction cells in this process, but need to think of a good task. Any ideas/references?

Network

Cited By

Projects

Projects (3)
Project
To test different retrograde tracers to see the inputs to particular structures and cell types: - monosynaptic mutated rabies tracing (Callaway et al.) - AAV2retro (Karpova et al.) Distant aim: to trace the inputs to a single neuron in combination with recording this cell in an awake mouse, as recently done in visual cortex (Margrie et al., Roska et al.).
Project
I aim to describe Alzheimer's Disease (AD) related changes in local field potential rhythmicity in the medial entorhinal cortex (MEC) in APP-PS1 mice, which are a commonly used mouse model of (some aspects of) AD. In AD, our knowledge of brain activity during navigation (and memory) is largely limited by the fact that measuring the brain requires bulky machines, so that we can only record during navigation in a virtual environment. Therefore, to allow more direct comparison with human studies, our recordings with silicon probes in the MEC of mice are performed as they run on an air-suspended ball whose movements are coupled to a virtual reality displayed on a series of surrounding computer screens. We hope this will help us understand how this structure is affected by AD-related pathology during a (virtual) navigation task, and possibly find early biomarkers that could be detected in the EEG of patients in the early stages of this disease.
Project
The medial septum (MS) provides inputs to virtually all structures of the hippocampal formation, including the parasubiculum (PaS) and medial entorhinal cortex (MEC). The PaS in turn provides one of the main inputs to the medial entorhinal cortex, specifically targeting layer 2. While activity in the MEC, particularly the periodic firing of grid cells, has been shown to depend on MS, it is unclear to what extent this might be related to indirect effects, eg via PaS. More generally, it is unclear exactly what kind of information the MEC receives from the PaS, which contains a range of navigation-related cell types more famously found in MEC, including grid, border, and head-direction cells. Even more generally, besides the idea that it is related to navigation and memory, the specific function of the PaS remains very unclear; its long thin shape has so far precluded any specific lesion studies. We are applying a range of methods including pharmacologic and chemogenetic manipulation in combination with behavioral testing and in vivo electrophysiology, but also optogenetics in vitro, to elucidate the role of this still enigmatic structure and its connections.