All events, All years

Brain control and readout at biologically relevant resolutions

Lecture
Date:
Monday, June 17, 2019
Hour: 11:00
Location:
Max and Lillian Candiotty Building
Dr. Or Shemesh
|
Postdoctoral Fellow, MIT Media lab and McGovern Institute for Brain Research, MIT

Understanding the neural basis of behavior requires studying the activity of neural networks. Within a neural network, single neurons can have different firing properties, different neural codes and different synaptic counterparts. Therefore, it will be useful to readout from the brain and control it at a single-cell resolution. However, until recently, single cell readout and control in the brain were not feasible. The first scientific problem we addressed, is this regard, was the low spatial resolution of light based neural activation. Opsins are genetically encoded light switches for neurons that cause neural firing, or inhibition, when illuminated (and are therefore called “opto-genetic” molecules). However, optogenetic experiments are biased by ‘crosstalk’: the accidental stimulation of dozens of cells other than the cell of interest during neuron photostimulation. This is caused by expression of optogenetic molecules through the entirety of the cells, from the round cell body (“soma”) to the elongated neural processes. Our solution was molecular-focusing: by limiting the powerful opsin CoChR to the cell body of the neuron, we discovered that we could excite the cell body of interest alone. This molecule, termed “somatic-CoChR” was stimulated with state of the art holographic stimulation to enable millisecond temporal control which can emulate actual brain activity. Thus, we achieved for the first time single cell optogenteic stimulation at sub millisecond temporal precision. A second challenge was imaging the activity of multiple cells at a single cell resolution. The most popular neural activity indicator is the genetically encoded calcium sensor GCaMP, due to its optical brightness and high sensitivity. However, the fluorescent signal originating from a cell body is contaminated with multiple other fluorescent signals that originate from neurites of neighboring cells. This leads to a variety of artifacts including non-physiological correlation between cells and an impaired ability to distinguish between signals coming from different cells. To solve this, we made a cell body-targeted GCaMP. We screened over 30 different targeting motifs for somatic localization of GCaMP, and termed the best one, in terms of somatic localization, “SomaGCaMP”. This molecule was tested in live mice and zebrafish and can report the activity of thousands of neurons at a single cell resolution. A third challenge was voltage imaging in the brain, since genetically encoded indicators still suffered from either low sensitivity, or from low brightness. To record voltage, we used nitrogen vacancy nanodiamonds, known to be both very bright and sensitive to electric fields. Our aim was to bring the nanodiamonds to the membrane so the large electric field created by the action potential could impinge upon them and change their fluorescence. By making the nanodiamonds hydrophobic through surface chemistry modification, and inserting them into micelles, we labeled neural membranes with monodisperse diamonds for hours. We are now in the process of assessing the sensitivity of the nanodiamonds to the membrane voltage. Altogether, thinking backwards from fundamental limitations in neuroscience is instrumental in deriving strategies to fix these limitations and study the brain. In the future, we will use similar approaches to study and heal brain disease, at single-cell and subcellular resolutions.

A Comprehensive Mechanistic Biological Theory of Brain Function

Lecture
Date:
Sunday, June 16, 2019
Hour: 11:00
Location:
Camelia Botnar Building
Prof. Ari Rappoport
|
The Rachel and Selim Benin School of Computer Science and Engineering The Hebrew University of Jerusalem

The brain is the target of intense scientific study, yet currently there is no theory of how it works at the system level. In this talk I will present the first such theory. The theory is biological and concrete, showing how motor and cognitive capacities arise from relatively understood biological entities. The main idea is that brain function is managed by a response (R) process whose structure is very similar to the process guiding the immune system. The brain has two instances of the R process, managing execution and need satisfaction. The stages of the execution process are implemented by different neural circuits, explaining the roles of cortical layers, the different types of inhibitory interneurons, hippocampal fields and basal ganglia paths. The stages of the need process are supported by different molecular agents, explaining the roles of dopamine, serotonin, ACh, opioids and oxytocin. The same execution process gives rise to hierarchical motor sequences, language, and imagery, while the need process explains feelings/emotions and consciousness in a mechanistic manner. The theory includes some aspects that are dramatically different from accepted accounts, e.g., the roles of basal ganglia paths, serotonin and opioids. The scope of the addressed phenomena is large, but they are all explained quite simply by the R process.

Memory In The Brain: From Learning To Forgetting

Conference
Date:
Tuesday, June 11, 2019
Hour: 08:30 - 18:00
Location:
David Lopatie Conference Centre

Homepage

Memory networks in the human brain

Lecture
Date:
Tuesday, June 4, 2019
Hour: 14:00 - 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Michael Kahana
|
Dept of Psychology University of Pennsylvania

Human memory function is highly variable, fluctuating between periods of high and low performance even within a given person. Neurosurgical patients with indwelling electrodes present a unique opportunity to study the neural correlates of this variability and to define both the features of neural activity at a given brain location and the functional connections between brain regions that predict variability in memory encoding and retrieval. Here, I will describe our recent efforts to characterize brain networks that support memory via correlative (passive neural recording) and causal (direct electrical stimulation) approaches. Throughout the brain, we find that low-frequency networks exhibit reduced local power but stronger functional connectivity during successful episodic encoding and retrieval. Furthermore, many canonical memory regions emerge as hubs of such low-frequency connections, including the lateral frontotemporal cortices, the parahippocampal gyrus – and within it – the entorhinal cortex. High-frequency bands (i.e. gamma, 30+ Hz) almost exclusively exhibit desynchronization during successful memory operations. We recently extended these correlative studies and used intracranial stimulation to ask whether functional connections imply causality. We confirmed that electrical stimulation evokes increases in theta power at remote regions, as predicted by the strength of low-frequency functional connections. This relation was strongest when stimulation occurred in or near white matter. These findings demonstrate the importance of low-frequency connectivity to episodic memory, integrating these findings over spatial scales and through causal and correlative approaches.

Multisensory perception: Exploring space and time

Lecture
Date:
Thursday, May 30, 2019
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. David I. Shore
|
Multisensory Perception Laboratory Dept of Psychology, Neuroscience & Behaviour McMaster University

Exploring multisensory interactions requires a definition for a single sense. As such, the first part of the talk with focus on the question of "how many senses are there?". Within this discussion, there are interactions between senses that form the mainstay of the multisensory literature. Two factors—space and time—form a foundation for considering when stimuli will be integrated. One series of experiments will focus on the resolution of conflicts between our internal reference frame and the external reference frame by examining the interaction of touch and proprioception in the crossed-hands TOJ deficit. The final section of the talk will explore the developmental trajectory for interactions between different primary modalities: vision, touch, and audition. Overall, the goal of the talk is to introduce the concept of multisensory integration and give the audience a sample of research questions ongoing in our lab. Light refreshments before the seminar

Stability and Plasticity of Chemosensory Stimulus Representations

Lecture
Date:
Tuesday, May 28, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Yoram Ben-Shaul
|
Dept of Medical Neurobiology, Faculty of Medicine Institute of Medical Research Israel Canada, Hebrew University of Jerusalem

The vomeronasal system is a chemosensory system devoted to processing cues from other organisms. In my talk I will describe a set of studies from our lab that aim to reveal how chemosensory information is represented by neuronal activity in the AOB (accessory olfactory bulb), the first brain region receiving vomeronasal inputs. After reviewing some of our published work on basic aspects of stimulus representations, I will describe unpublished work in which we explore neuronal correlates of behavioral imprinting, reproductive-state dependent processing, and changes in the genetic background of the subject organism. Taken together, these studies point at a high degree of stability of stimulus representations at the level of the AOB. Finally, I will show that despite its presumed role in processing innately relevant cues, the vomeronasal system has considerable capacity to form novel stimulus response associations, providing further support for the idea that responses to innately relevant cues can be dramatically altered as a result of experience.

Neuronal membrane proteasomes and their released extracellular peptides modulate nervous system signaling

Lecture
Date:
Sunday, May 26, 2019
Hour: 11:00 - 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Seth S. Margolis
|
Dept of Biological Chemistry The Johns Hopkins University School of Medicine, Baltimore MD

In mammals, activity-dependent changes in neuronal function require coordinated regulation of the protein synthesis and protein degradation machinery. However, the biochemical evidence for this balance and coordination is largely lacking. To investigate this we initially used acute metabolic radiolabeling of stimulated primary mouse neurons to follow the fate of polypeptides being newly synthesized. We observed polypeptides being newly translated exclusively during neuronal stimulation were rapidly degraded by the neuronal membrane proteasome (NMP) and not the cytosolic proteasome. This turnover correlated with enhanced production of NMP-derived peptides into the extracellular space which have the capacity to mediate neuronal signaling in part through NMDA receptors. Using in-depth, global, and unbiased mass spectrometry, we identified the nascent protein substrates of the NMP. Among these substrates, we found that immediate-early gene products c-Fos and Npas4 were targeted to the NMP during ongoing activity-dependent protein synthesis. Moreover, we found that turnover of nascent polypeptides and not full-length proteins through the NMP occurred independent of canonical ubiquitylation pathways. We propose that these findings generally define a neuronal activity-induced protein homeostasis program of coordinated protein synthesis and degradation through the NMP. This generates a new modality of neuronal signaling in the form of extracellular peptides with potential significance for our understanding of nervous system development and function.

Mesoscale dissection of neuronal populations underlying complex behaviors

Lecture
Date:
Tuesday, May 21, 2019
Hour: 14:00 - 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Ariel Gilad
|
Brain Research Institute, University of Zurich ELSC for Brain Sciences, The Hebrew University of Jerusalem

One of the fundamental functions of the brain is to integrate incoming sensory stimuli, perceive and associate these integrations with internal representations, and make fast and reliable decisions and actions. Although these processes have been extensively studied, we are still missing a comprehensive understanding of the exact spatiotemporal dynamics at a mesoscale level, i.e. at the neuronal population level spanning many cortical and sub-cortical areas. In my opinion, the key to understanding these processes is to measure from large populations of neurons within a single trial as a subject performs a complex behavior. In my talk, I will present a variety of evidence from behaving mice backing up this claim. In one of the projects, we imaged calcium signals from the whole dorsal cortex of mice performing a whisker-based texture discrimination task with a short-term memory component. Mice use different behavioral strategies to solve the task either deploying an active strategy — engaging their body and whiskers towards the approaching texture — or passively awaited the touch. Based on this strategy, short-term memory was located in frontal secondary motor cortex (M2) in active mice whereas in a newly identified posterior area (P) in passive mice. Optogenetic perturbation of these areas impaired performance specifically in the associated strategy. In some cases, mice overcame the perturbation by switching to the alternative strategy. Thus, depending on behavioral strategy within single trials, cortical population activity is routed differentially to hold information either frontally or posteriorly before converging to similar action. Additional projects, using different tasks, neuronal subtypes and during learning highlight the importance of observing and dissecting mesoscale dynamics during complex behaviors.

Sex, alcohol and fly mind

Lecture
Date:
Tuesday, May 7, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Galit Ophir
|
Faculty of Life Sciences Bar-Ilan University

Living in a social environment involves diverse types of interactions between members of the same species that are essential for the health, survival, and reproduction of animals. The intricate nature of social interaction requires the ability to identify and recognize other members of the group in the right context, season, sex, age and reproductive state, and to respond appropriately to different social encounters.We study mechanisms that shape social interaction in Drosophila melanogaster and investigate the ways by which social interaction modulates motivational states and leads to different action selection in subsequent social encounters.

A century-old assumption regarding neurons and brain learning is undermined by new types of experiments

Lecture
Date:
Tuesday, April 30, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ido Kanter
|
Dept of Physics, Bar-Ilan University

According to the long-lasting computational scheme each neuron sums the incoming electrical signals via its dendrites and when the membrane potential reaches a certain threshold the neuron typically generates a spike. We present three types of experiments indicating that each neuron functions as a collection of independent threshold units, where the neuron is activated following the origin of the arriving signals. In addition, experimental and theoretical results reveal a new underlying mechanism for the fast brain learning process, dendritic learning, as opposed to learning which is based solely on slow synaptic plasticity. The learning occurs in closer proximity to the neuron, dendritic strengths are self-oscillating, and weak synapses play a key role in the dynamics.

Pages

All events, All years

Brain control and readout at biologically relevant resolutions

Lecture
Date:
Monday, June 17, 2019
Hour: 11:00
Location:
Max and Lillian Candiotty Building
Dr. Or Shemesh
|
Postdoctoral Fellow, MIT Media lab and McGovern Institute for Brain Research, MIT

Understanding the neural basis of behavior requires studying the activity of neural networks. Within a neural network, single neurons can have different firing properties, different neural codes and different synaptic counterparts. Therefore, it will be useful to readout from the brain and control it at a single-cell resolution. However, until recently, single cell readout and control in the brain were not feasible. The first scientific problem we addressed, is this regard, was the low spatial resolution of light based neural activation. Opsins are genetically encoded light switches for neurons that cause neural firing, or inhibition, when illuminated (and are therefore called “opto-genetic” molecules). However, optogenetic experiments are biased by ‘crosstalk’: the accidental stimulation of dozens of cells other than the cell of interest during neuron photostimulation. This is caused by expression of optogenetic molecules through the entirety of the cells, from the round cell body (“soma”) to the elongated neural processes. Our solution was molecular-focusing: by limiting the powerful opsin CoChR to the cell body of the neuron, we discovered that we could excite the cell body of interest alone. This molecule, termed “somatic-CoChR” was stimulated with state of the art holographic stimulation to enable millisecond temporal control which can emulate actual brain activity. Thus, we achieved for the first time single cell optogenteic stimulation at sub millisecond temporal precision. A second challenge was imaging the activity of multiple cells at a single cell resolution. The most popular neural activity indicator is the genetically encoded calcium sensor GCaMP, due to its optical brightness and high sensitivity. However, the fluorescent signal originating from a cell body is contaminated with multiple other fluorescent signals that originate from neurites of neighboring cells. This leads to a variety of artifacts including non-physiological correlation between cells and an impaired ability to distinguish between signals coming from different cells. To solve this, we made a cell body-targeted GCaMP. We screened over 30 different targeting motifs for somatic localization of GCaMP, and termed the best one, in terms of somatic localization, “SomaGCaMP”. This molecule was tested in live mice and zebrafish and can report the activity of thousands of neurons at a single cell resolution. A third challenge was voltage imaging in the brain, since genetically encoded indicators still suffered from either low sensitivity, or from low brightness. To record voltage, we used nitrogen vacancy nanodiamonds, known to be both very bright and sensitive to electric fields. Our aim was to bring the nanodiamonds to the membrane so the large electric field created by the action potential could impinge upon them and change their fluorescence. By making the nanodiamonds hydrophobic through surface chemistry modification, and inserting them into micelles, we labeled neural membranes with monodisperse diamonds for hours. We are now in the process of assessing the sensitivity of the nanodiamonds to the membrane voltage. Altogether, thinking backwards from fundamental limitations in neuroscience is instrumental in deriving strategies to fix these limitations and study the brain. In the future, we will use similar approaches to study and heal brain disease, at single-cell and subcellular resolutions.

A Comprehensive Mechanistic Biological Theory of Brain Function

Lecture
Date:
Sunday, June 16, 2019
Hour: 11:00
Location:
Camelia Botnar Building
Prof. Ari Rappoport
|
The Rachel and Selim Benin School of Computer Science and Engineering The Hebrew University of Jerusalem

The brain is the target of intense scientific study, yet currently there is no theory of how it works at the system level. In this talk I will present the first such theory. The theory is biological and concrete, showing how motor and cognitive capacities arise from relatively understood biological entities. The main idea is that brain function is managed by a response (R) process whose structure is very similar to the process guiding the immune system. The brain has two instances of the R process, managing execution and need satisfaction. The stages of the execution process are implemented by different neural circuits, explaining the roles of cortical layers, the different types of inhibitory interneurons, hippocampal fields and basal ganglia paths. The stages of the need process are supported by different molecular agents, explaining the roles of dopamine, serotonin, ACh, opioids and oxytocin. The same execution process gives rise to hierarchical motor sequences, language, and imagery, while the need process explains feelings/emotions and consciousness in a mechanistic manner. The theory includes some aspects that are dramatically different from accepted accounts, e.g., the roles of basal ganglia paths, serotonin and opioids. The scope of the addressed phenomena is large, but they are all explained quite simply by the R process.

Memory networks in the human brain

Lecture
Date:
Tuesday, June 4, 2019
Hour: 14:00 - 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Michael Kahana
|
Dept of Psychology University of Pennsylvania

Human memory function is highly variable, fluctuating between periods of high and low performance even within a given person. Neurosurgical patients with indwelling electrodes present a unique opportunity to study the neural correlates of this variability and to define both the features of neural activity at a given brain location and the functional connections between brain regions that predict variability in memory encoding and retrieval. Here, I will describe our recent efforts to characterize brain networks that support memory via correlative (passive neural recording) and causal (direct electrical stimulation) approaches. Throughout the brain, we find that low-frequency networks exhibit reduced local power but stronger functional connectivity during successful episodic encoding and retrieval. Furthermore, many canonical memory regions emerge as hubs of such low-frequency connections, including the lateral frontotemporal cortices, the parahippocampal gyrus – and within it – the entorhinal cortex. High-frequency bands (i.e. gamma, 30+ Hz) almost exclusively exhibit desynchronization during successful memory operations. We recently extended these correlative studies and used intracranial stimulation to ask whether functional connections imply causality. We confirmed that electrical stimulation evokes increases in theta power at remote regions, as predicted by the strength of low-frequency functional connections. This relation was strongest when stimulation occurred in or near white matter. These findings demonstrate the importance of low-frequency connectivity to episodic memory, integrating these findings over spatial scales and through causal and correlative approaches.

Multisensory perception: Exploring space and time

Lecture
Date:
Thursday, May 30, 2019
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. David I. Shore
|
Multisensory Perception Laboratory Dept of Psychology, Neuroscience & Behaviour McMaster University

Exploring multisensory interactions requires a definition for a single sense. As such, the first part of the talk with focus on the question of "how many senses are there?". Within this discussion, there are interactions between senses that form the mainstay of the multisensory literature. Two factors—space and time—form a foundation for considering when stimuli will be integrated. One series of experiments will focus on the resolution of conflicts between our internal reference frame and the external reference frame by examining the interaction of touch and proprioception in the crossed-hands TOJ deficit. The final section of the talk will explore the developmental trajectory for interactions between different primary modalities: vision, touch, and audition. Overall, the goal of the talk is to introduce the concept of multisensory integration and give the audience a sample of research questions ongoing in our lab. Light refreshments before the seminar

Stability and Plasticity of Chemosensory Stimulus Representations

Lecture
Date:
Tuesday, May 28, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Yoram Ben-Shaul
|
Dept of Medical Neurobiology, Faculty of Medicine Institute of Medical Research Israel Canada, Hebrew University of Jerusalem

The vomeronasal system is a chemosensory system devoted to processing cues from other organisms. In my talk I will describe a set of studies from our lab that aim to reveal how chemosensory information is represented by neuronal activity in the AOB (accessory olfactory bulb), the first brain region receiving vomeronasal inputs. After reviewing some of our published work on basic aspects of stimulus representations, I will describe unpublished work in which we explore neuronal correlates of behavioral imprinting, reproductive-state dependent processing, and changes in the genetic background of the subject organism. Taken together, these studies point at a high degree of stability of stimulus representations at the level of the AOB. Finally, I will show that despite its presumed role in processing innately relevant cues, the vomeronasal system has considerable capacity to form novel stimulus response associations, providing further support for the idea that responses to innately relevant cues can be dramatically altered as a result of experience.

Neuronal membrane proteasomes and their released extracellular peptides modulate nervous system signaling

Lecture
Date:
Sunday, May 26, 2019
Hour: 11:00 - 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Seth S. Margolis
|
Dept of Biological Chemistry The Johns Hopkins University School of Medicine, Baltimore MD

In mammals, activity-dependent changes in neuronal function require coordinated regulation of the protein synthesis and protein degradation machinery. However, the biochemical evidence for this balance and coordination is largely lacking. To investigate this we initially used acute metabolic radiolabeling of stimulated primary mouse neurons to follow the fate of polypeptides being newly synthesized. We observed polypeptides being newly translated exclusively during neuronal stimulation were rapidly degraded by the neuronal membrane proteasome (NMP) and not the cytosolic proteasome. This turnover correlated with enhanced production of NMP-derived peptides into the extracellular space which have the capacity to mediate neuronal signaling in part through NMDA receptors. Using in-depth, global, and unbiased mass spectrometry, we identified the nascent protein substrates of the NMP. Among these substrates, we found that immediate-early gene products c-Fos and Npas4 were targeted to the NMP during ongoing activity-dependent protein synthesis. Moreover, we found that turnover of nascent polypeptides and not full-length proteins through the NMP occurred independent of canonical ubiquitylation pathways. We propose that these findings generally define a neuronal activity-induced protein homeostasis program of coordinated protein synthesis and degradation through the NMP. This generates a new modality of neuronal signaling in the form of extracellular peptides with potential significance for our understanding of nervous system development and function.

Mesoscale dissection of neuronal populations underlying complex behaviors

Lecture
Date:
Tuesday, May 21, 2019
Hour: 14:00 - 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Ariel Gilad
|
Brain Research Institute, University of Zurich ELSC for Brain Sciences, The Hebrew University of Jerusalem

One of the fundamental functions of the brain is to integrate incoming sensory stimuli, perceive and associate these integrations with internal representations, and make fast and reliable decisions and actions. Although these processes have been extensively studied, we are still missing a comprehensive understanding of the exact spatiotemporal dynamics at a mesoscale level, i.e. at the neuronal population level spanning many cortical and sub-cortical areas. In my opinion, the key to understanding these processes is to measure from large populations of neurons within a single trial as a subject performs a complex behavior. In my talk, I will present a variety of evidence from behaving mice backing up this claim. In one of the projects, we imaged calcium signals from the whole dorsal cortex of mice performing a whisker-based texture discrimination task with a short-term memory component. Mice use different behavioral strategies to solve the task either deploying an active strategy — engaging their body and whiskers towards the approaching texture — or passively awaited the touch. Based on this strategy, short-term memory was located in frontal secondary motor cortex (M2) in active mice whereas in a newly identified posterior area (P) in passive mice. Optogenetic perturbation of these areas impaired performance specifically in the associated strategy. In some cases, mice overcame the perturbation by switching to the alternative strategy. Thus, depending on behavioral strategy within single trials, cortical population activity is routed differentially to hold information either frontally or posteriorly before converging to similar action. Additional projects, using different tasks, neuronal subtypes and during learning highlight the importance of observing and dissecting mesoscale dynamics during complex behaviors.

Sex, alcohol and fly mind

Lecture
Date:
Tuesday, May 7, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Galit Ophir
|
Faculty of Life Sciences Bar-Ilan University

Living in a social environment involves diverse types of interactions between members of the same species that are essential for the health, survival, and reproduction of animals. The intricate nature of social interaction requires the ability to identify and recognize other members of the group in the right context, season, sex, age and reproductive state, and to respond appropriately to different social encounters.We study mechanisms that shape social interaction in Drosophila melanogaster and investigate the ways by which social interaction modulates motivational states and leads to different action selection in subsequent social encounters.

A century-old assumption regarding neurons and brain learning is undermined by new types of experiments

Lecture
Date:
Tuesday, April 30, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ido Kanter
|
Dept of Physics, Bar-Ilan University

According to the long-lasting computational scheme each neuron sums the incoming electrical signals via its dendrites and when the membrane potential reaches a certain threshold the neuron typically generates a spike. We present three types of experiments indicating that each neuron functions as a collection of independent threshold units, where the neuron is activated following the origin of the arriving signals. In addition, experimental and theoretical results reveal a new underlying mechanism for the fast brain learning process, dendritic learning, as opposed to learning which is based solely on slow synaptic plasticity. The learning occurs in closer proximity to the neuron, dendritic strengths are self-oscillating, and weak synapses play a key role in the dynamics.

Brain cell type analysis and why it matters for disease

Lecture
Date:
Tuesday, April 16, 2019
Hour: 14:00
Location:
Camelia Botnar Building
Prof. Jens Hjerling-Leffler
|
Dept of Medical Biochemistry and Biophysics Karolinska Institute, Sweden

Cellular complexity in the brain has been a central area of study since the birth of cellular neuroscience over a hundred years ago. Several different classification systems have been put forward based on emerging techniques. It is still largely unclear if and how the classification system produced using recent single-cell transcriptomics corresponds to previous classification systems. The interneurons of the hippocampus has been extensively characterised on physiological and morphological basis and we used this classification as a basis to compare single-cell RNA sequencing data from the CA1 hippocampus. We show, using the in situ sequencing technique “pciSeq” that the predictions made from scRNAseq data corresponds existing classification. Furthermore, we leverage the rich data from scRNAseq and combined it with GWAS data from patients to begin to elucidate the cellular origin of genetic heritability of brain disorders. Although many of these disorders are genetically complex it seems that specific and sometimes non-overlapping cell types underlie the ethology of these disorders. For instance we show a largely ignored role of oligodendrocytes in Parkinson’s disease which can be confirmed in patient material. This proves the feasibility to link modern transcriptomics with genetics to leverage the recent advances in understanding of genetic structure of brain disorders to yield actionable targets.

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