Bakgrunn og aktiviteter
Professor of Medicine and leader of the Kentros research group at the Kavli Institute of Systems Neuroscience, NTNU.
Kentros’ laboratory takes advantage of his dual molecular and neurophysiological background by combining the anatomical specificity of molecular genetics with in vivo electrophysiological recordings and anatomical analysis.
The lab uses mice capable of driving the expression of transgenes in particular subsets of neurons in brain areas involved in learning and memory to determine their precise connectivity and to modulate their neural activity while recording from other cell types. In this way, the lab investigates the anatomical and functional circuitry underlying learning and memory.
Using molecular genetic techniques to investigate the neural circuitry of memory
The one feature above all that differentiates the mammalian brain from from all other biological structures is its anatomical complexity: the human brain contains an estimated 100 billion neurons, each connected to an average of 10,000 other neurons and organized into innumerable distinct cell types. One cannot understand electronic circuits without a detailed circuit diagram and the ability to manipulate single circuit elements while recording from others. Similarly, it is impossible to fully understand brain function without being able to identify and manipulate specific neuronal cell types while recording from other circuit elements. For this reason, my laboratory both performs in vivo recordings from awake, behaving animals, and attempts to generate novel molecular genetic tools capable of driving transgene in specific neuronal cell types, particularly in those parts of the brain involved in learning and memory. Recent years have seen remarkable advances in molecular genetic tools for the elucidation and manipulation of neural circuits, but the means to deliver such transgenes with the requisite specificity has lagged far behind. One can only address the manifest complexity of the brain by co-oping the genetic machinery which underlies it, but while most genes are expressed in the brain, they are unfortunately almost always expressed in multiple cell types. My laboratory has recently taken a novel tactic to address this problem by using transcriptional cis-regulatory sequences specific to particular microdissected brain regions to drive transgene expression in particular cell types of that region, an approach we call Enhancer-Driven Gene Expression (EDGE). Our recent work has shown that EDGE yields anatomical specificity of transgene expression far surpassing that of the parent gene... i.e. one can obtain high degrees of anatomical specificity from nonspecific genes. Moreover, these enhancers are typically small enough to fit inside viral vectors, obviating the need for transgenic animals and opening up such anatomically-specific approaches to any species. This last feature not only will bring circuit-specific manipulations to any model species, it has the promise to open up entirely new circuit-specific therapeutic avenues to pathologies of the brain.
Vitenskapelig, faglig og kunstnerisk arbeid
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- (2022) Validation of Functional Connectivity of Engineered Neuromuscular Junction With Recombinant Monosynaptic Pseudotyped ΔG-Rabies Virus Tracing. Frontiers in Integrative Neuroscience. vol. 16.
- (2022) Single Cell Transcriptomic and Chromatin Profiles Suggest Layer Vb Is the Only Layer With Shared Excitatory Cell Types in the Medial and Lateral Entorhinal Cortex. Frontiers in Neural Circuits. vol. 15.
- (2022) Social Learning of a Spatial Task by Observation Alone. Frontiers in Behavioral Neuroscience. vol. 16.
- (2022) Lowering levels of reelin in entorhinal cortex layer II-neurons results in lowered levels of intracellular amyloid-β. bioRxiv.
- (2021) Multiplexing viral approaches to the study of the neuronal circuits. Journal of Neuroscience Methods. vol. 357.
- (2021) Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex. eLIFE.
- (2020) Enhancer-Driven Gene Expression (EDGE) enables the generation of cell type specific tools for the analysis of neural circuits. Neuroscience research. vol. 152.
- (2020) Enhancer-Driven Gene Expression (EDGE) Enables the Generation of Viral Vectors Specific to Neuronal Subtypes. iScience. vol. 23 (3).
- (2019) Modelling functional human neuromuscular junctions in a differentially-perturbable microfluidic environment, validated through recombinant monosynaptic pseudotyped ΔG-rabies virus tracing. BioRxiv.
- (2018) Marked Diversity of Unique Cortical Enhancers Enables Neuron-Specific Tools by Enhancer-Driven Gene Expression. Current Biology. vol. 28 (13).
- (2018) Inhibitory Connectivity Dominates the Fan Cell Network in Layer II of Lateral Entorhinal Cortex. Journal of Neuroscience. vol. 38 (45).
- (2018) Functional properties of stellate cells in medial entorhinal cortex layer II. eLIFE. vol. 7.
- (2017) A Novel Mechanism for the Grid-to-Place Cell Transformation Revealed by Transgenic Depolarization of Medial Entorhinal Cortex Layer II. Neuron. vol. 93 (6).
- (2017) TU-tagging: A method for identifying layer-enriched neuronal genes in developing mouse visual cortex. eNeuro. vol. 4 (5).
- (2014) Role of self-generated odor cues in contextual representation. Hippocampus. vol. 24 (8).
- (2014) Beyond the bolus: Transgenic tools for investigating the neurophysiology of learning and memory. Learning & memory (Cold Spring Harbor, N.Y.). vol. 21 (10).
- (2014) Grid cells and cortical representation. Nature Reviews Neuroscience. vol. 15 (7).
- (2014) Perceptual gap detection is mediated by gap termination responses in auditory cortex. Current Biology. vol. 24 (13).
- (2013) Transgenically Targeted Rabies Virus Demonstrates a Major Monosynaptic Projection from Hippocampal Area CA2 to Medial Entorhinal Layer II Neurons. Journal of Neuroscience. vol. 33 (37).
- (2009) What is remembered? Role of attention on the encoding and retrieval of hippocampal representations. Journal of Physiology. vol. 587 (12).