2019
All events, 2019
Learning and retaining representations in redundant networks
Lecture
Thursday, November 7, 2019
Hour: 11:00 - 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Learning and retaining representations in redundant networks
Information Engineering and Medical Neuroscience
University of Cambridge, UK
Neuronal networks have many tunable parameters such as synaptic strengths that are shaped during learning of a task. The number of degrees of freedom for representing a task can vastly exceed the minimum required for good performance. I will describe recent work that explores the consequences of such additional ‘redundant’ degrees of freedom for learning and for task representation. We find that additional redundancy in network parameters can make a fixed task easier to learn and compensate for deficiencies in learning rules. However, we also find that in a biologically relevant setting where synapses are subject to unavoidable noise there is an upper limit to the level of useful redundancy in a network, suggesting an optimal network size for a given task.
Collective Conflict Resolution in Groups on the Move
Lecture
Tuesday, November 5, 2019
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Collective Conflict Resolution in Groups on the Move
Prof. Nir Gov
Dept of Chemical and Biological Physics
Faculty of Chemistry, WIS
Collective decision-making regarding direction of travel is observed during natural motion of animal and cellular groups. This phenomenon is exemplified, in the simplest case, by a group that contains two informed subgroups that hold conflicting preferred directions of motion. Under such circumstances, simulations, subsequently supported by experimental data with birds and primates, have demonstrated that the resulting motion is either towards a compromise direction or towards one of the preferred targets (even when the two subgroups are equal in size). However, the nature of this transition is not well understood. We present a theoretical study that combines simulations and a spin model for mobile animal groups. This allows us to identify the nature of this transition at a critical angular difference between the two preferred directions: in both flocking and spin models the transition coincides with the change in the group dynamics from Brownian to persistent collective motion. The groups undergo this transition as the number of uninformed individuals (those in the group that do not exhibit a directional preference) increases, which acts as an inverse of the temperature (noise) of the spin model. When the two informed subgroups are not equal in size, there is a tendency for the group to reach the target preferred by the larger subgroup. We find that the spin model captures effectively the essence of the collective decision-making transition and allows us to reveal a noise-dependent trade-off between the decision-making speed and the ability to achieve majority (democratic) consensus.
"Sporadic Alzheimer's disease – does it start with altered ubiquitin signaling?”
Lecture
Tuesday, October 29, 2019
Hour: 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
"Sporadic Alzheimer's disease – does it start with altered ubiquitin signaling?”
Prof. Michael H. Glickman
Department of Biology, Technion, Haifa
With our rapidly aging population, Alzheimer’s disease (AD) is often considered the plague of the 21st century. While much is known regarding the direct genetic mutations that trigger the rare familial form of the disease (FAD), molecular mechanisms driving the emergence of late-onset sporadic AD (SAD) remain elusive. A distinctively human predicament, AD is a protein-based disease characterized by toxic protein build up in the brain. The principal mechanisms for protein turnover or removal are dependent on ubiquitin. We will describe evidence that interference with ubiquitin signalling in a 3-dimentional human neuronal culture is sufficient to cause the two pathological hallmarks of AD (A plaques and neurofibrillary tangles), even in the absence of any familial mutations. By utilizing this platform, we specifically demonstrate that attenuated ubiquitin-dependent turnover leads to elevated levels of the Amyloid Precursor Protein (APP), enhanced secretion of the toxic amyloid-β42 peptide, and extra-cellular amyloid plaque build-up. Furthermore, we demonstrate that impaired ubiquitin signalling is a common feature of different human and murine models of AD, whereas overcoming this impairment is sufficient to decrease formation of A plaques and neurofibrillary tangles in an experimental model of FAD. To summarise, our work uncovers a role for ubiquitin during the early “cellular phase” of neurodegeneration that underlies emergence and progression of AD, providing hope that tweaking components of the ubiquitin-proteasome system has the potential to decrease risk for developing AD pathology, opening up new therapeutic approaches.
Neural and emotional states under social interactions
Lecture
Thursday, October 10, 2019
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Neural and emotional states under social interactions
Raviv Pryluk (PhD Thesis Defense)
Rony Paz Lab, Dept of Neurobiology, WIS
Primates live in large and complex social groups. It has been argued that this has led to evolutionary pressure on the brain and that there are networks that have been evolved to play an important role in social cognition and behaviors. Social deficits are widely known in many brain disorders such as autism and anxiety. Here we focused on two brain areas that were shown to play a crucial role in social interactions – the amygdala and the anterior-cingulate-cortex (ACC). Our goal was to understand the neural codes in these two regions and especially under social interactions:
1. Computational techniques that allow the comparison of on-going neural activity across these brain regions and species based on information theory measures was developed. We found that human neurons better utilize information capacity (efficient coding) than macaque neurons in both regions, and that ACC neurons are more efficient than amygdala neurons, in both species. In contrast, we found more overlap in the neural vocabulary and more synchronized activity (robustness coding) in monkeys in both regions, and in the amygdala of both species. Our findings demonstrate a tradeoff between robustness and efficiency across species and regions. We suggest that this tradeoff can contribute to the differential cognitive functions between species, and can underlie the complementary roles of the amygdala and the ACC. It can also contribute to the fragility underlying human psychopathologies. For more, see https://www.sciencedirect.com/science/article/pii/S0092867418316465
2. A novel electrophysiology experiment that induced real and live social interactions between humans and primates was conducted. In each daily session, we recorded neural responses in monkeys to the eye-gaze, direct or averted, of human intruders, and compared it with the responses to valence conditioning, aversive and appetitive. We found that the primate amygdala, but not the ACC, encodes eye-gaze; this coding is shared with valence coding through two mechanisms – “shared-activity” at the expectation epoch (conditioned stimulus, CS) and “shared-intensity” after the outcome (unconditioned stimulus, US). These shared mechanisms can open an indirect window for future therapy. For more, see https://www.biorxiv.org/content/10.1101/736462v1
3. We developed behavioral methods and algorithms to evaluate primates’ emotional states, using the analysis of facial expressions and a number of physiological parameters such as heart rate and respiratory rate. The primates’ emotional state evaluation will be the substrate for future studies that will investigate the neural correlates of these states.
Tonic GABAA receptor mediated conductance at cellular and network levels
Lecture
Monday, September 23, 2019
Hour: 14:00 - 15:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Tonic GABAA receptor mediated conductance at cellular and network levels
Prof. Alexey Semyanov
Head, Dept of Molecular Neurobiology, Institute of BioOrganic Chemistry, Moscow
GABAA receptors mediate two forms of signaling in the brain: phasic and tonic. Phasic signaling (e.g., IPSCs) is mediated by synaptic GABAA receptors, while tonic signaling (e.g., tonic current or tonic conductance) is mediated by extrasynaptic GABAA receptors. Tonic current is expressed in a cell-type specific manner and is mediated by heterogeneous and plastic GABAA receptors. These receptors are activated by ambient GABA that originates from vesicular and non-vesicular sources and is regulated by different GABA transporter systems.
Tonic GABAA conductance is commonly referred as tonic inhibition. We found that ambient GABA can actually excite adult hippocampal interneurons. In these cells, the GABAA reversal potential is depolarizing, making baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Because hippocampal interneurons are the key to setting the network rhythms this mechanism allows bidirectional control of network synchronization by tonic GABAA receptor-mediated signaling.
We also show that tonic GABAA conductance decreases the membrane time constant (τm) and improves the temporal fidelity of EPSP-spike coupling. Long-term potentiation (LTP) induced by different stimulation patterns is differently affected by tonic GABAA conductance.
Our findings thus point to an important role of extrasynaptic signaling mediated by GABAA receptors in brain computations.
Intracranial electrophysiology of speech perception and production
Lecture
Monday, August 12, 2019
Hour: 13:30 - 14:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Intracranial electrophysiology of speech perception and production
Dr. Adeen Flinker,Naomi Moses
NYU Langone, Dept of Neurology
For many decades, the neurobiological basis of language has been dominated by a conceptually dichotomous model in which speech perception is supported by Wernicke’s area in the temporal lobe and speech production is supported by Broca’s area in the frontal lobe. This model has been challenged by lesion and neuroimaging studies suggesting a more complex network of cortical structures supporting language. Many of the questions remaining in the field require a fine-grained temporal resolution together with spatial specificity in order to assay the dynamics of speech. Here I will introduce a series of studies employing direct electrocorticographic (ECoG) recordings in humans, illuminating the dynamics and cascade of neural events from perception to production of speech.
Cytokines as neuromodulators: How immunity affects brain function
Lecture
Thursday, June 27, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Cytokines as neuromodulators: How immunity affects brain function
Prof. Jonathan Kipnis
Center for Brain Immunology and Glia (BIG), Dept of Neuroscience University of Virginia, Charlottesville, VA
Immune cells and their derived molecules have major impact on brain function, but despite the robust influence on brain function, peripheral immune cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between immunity and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place and through which it impacts brain function. Unique sub-types of immune cells within meningeal spaces are producing certain sets of cytokines that impact specific behaviors. Three main cytokines and their neuromodulatory functions will be discussed in social, learning and risk-taking behaviors.
The Role of DOC2B in Vesicle Fusion and Asynchronous Neurotransmitter Release
Lecture
Tuesday, June 25, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
The Role of DOC2B in Vesicle Fusion and Asynchronous Neurotransmitter Release
Prof. Uri Ashery
Sagol School of Neuroscience and School of Neurobiology,
Biochemistry and Biophysics,
Life Sciences Faculty,
Tel Aviv University
DOC2B is a high-affinity Ca2+ sensor, which translocates from the cytosol to the plasma membrane (PM) upon Ca2+ elevation and regulates exocytosis by promoting priming and fusion. Its interaction with the PM depends both on calcium and on its C2 domains binding to phosphoinositides (PI(4,5)P2) at the PM. In the lecture, I will move from the level of protein structure and its targeting to PI(4,5)P2 via its effect on vesicle fusion in chromaffin cells up to its involvement in asynchronous release in neurons and its effects on neuronal network activity.
Environmental affordances and the neural representation of complex space
Lecture
Monday, June 17, 2019
Hour: 16:00 - 17:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Environmental affordances and the neural representation of complex space
Prof. Kate Jeffery
University College London
Externally and internally induced arousal states modify spontaneous and evoked synaptic activities in the mouse somatosensory cortex
Lecture
Monday, June 17, 2019
Hour: 13:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Externally and internally induced arousal states modify spontaneous and evoked synaptic activities in the mouse somatosensory cortex
Akiva Rapaport (PhD Thesis Defense)
Ilan Lampl Lab, Dept of Neurobiology, WIS
Behavioral states, such as arousal and attention are defined by a set of psychological and physiological variables. They have profound effects on sensation, perception, learning, and cognition. In the brain, global states are characterized by distinct cortical and hippocampal EEG patterns. These changes that are clearly observed in the local field potential (LFP) are also evident in network and cellular dynamics. At the population level, the more active states are manifested as asynchronous neuronal firing between neighboring cells. At the cellular level, the membrane potential during active states is characterized by a continuous depolarized state, high synaptic ac! tivity, reduced variance and reduced membrane potential correlations between cells. In recent years it has been demonstrated in rodents that pupil size is a robust indicator of a range of neural activity from neuromodulator release to cortical neuronal membrane potential.
There has been some debate in the field regarding to what extent the effects of locomotion on cortical dynamics are due to arousal and what can be attributed to locomotion. Furthermore, in some studies cortical dynamics were evaluated while the animals transitioned spontaneously between states and in others, states of arousal were externally induced. Additionally, different effects have been reported in the auditory and visual cortex. Therefore, we wanted to more finely differentiate between different states and evaluate the effect of state on the somatosensory cortex.
To accomplish this we conducted intracellular recordings in the barrel cortex as well as extracellular LFP recordings in Layer IV of the barrel cortex in awake head fixed mice. We monitored pupil size as an indicator for state of arousal as well as tracking locomotion.
We found that there is a significant correlation between membrane potential of cells in barrel cortex and pupil size. Neurons were significantly more depolarized as the animal was in a greater state of arousal. This change was not affected by the mode of inducement of arousal, be it a spontaneous transition into a state of arousal or one externally induced. However, the effect was abolished by the occurrence of locomotion.
We also found that responses to sensory stimuli are increased during a state of arousal but not in a state of hyper-arousal. Inducing the state externally minimized this effect and if the animal is locomoting then the increase in sensory responses is abolished.
We further found that when the animal is in a greater state of arousal there is less synchronization as indicated by the decrease in correlation between membrane potential and LFP. Even more startlingly, we found that the polarity of the cross-correlation was reversed during hyperarousal. This would strongly suggest a reorganization of the laminar network across different states.
Pages
2019
All events, 2019
Learning and retaining representations in redundant networks
Lecture
Thursday, November 7, 2019
Hour: 11:00 - 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Learning and retaining representations in redundant networks
Information Engineering and Medical Neuroscience
University of Cambridge, UK
Neuronal networks have many tunable parameters such as synaptic strengths that are shaped during learning of a task. The number of degrees of freedom for representing a task can vastly exceed the minimum required for good performance. I will describe recent work that explores the consequences of such additional ‘redundant’ degrees of freedom for learning and for task representation. We find that additional redundancy in network parameters can make a fixed task easier to learn and compensate for deficiencies in learning rules. However, we also find that in a biologically relevant setting where synapses are subject to unavoidable noise there is an upper limit to the level of useful redundancy in a network, suggesting an optimal network size for a given task.
Collective Conflict Resolution in Groups on the Move
Lecture
Tuesday, November 5, 2019
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Collective Conflict Resolution in Groups on the Move
Prof. Nir Gov
Dept of Chemical and Biological Physics
Faculty of Chemistry, WIS
Collective decision-making regarding direction of travel is observed during natural motion of animal and cellular groups. This phenomenon is exemplified, in the simplest case, by a group that contains two informed subgroups that hold conflicting preferred directions of motion. Under such circumstances, simulations, subsequently supported by experimental data with birds and primates, have demonstrated that the resulting motion is either towards a compromise direction or towards one of the preferred targets (even when the two subgroups are equal in size). However, the nature of this transition is not well understood. We present a theoretical study that combines simulations and a spin model for mobile animal groups. This allows us to identify the nature of this transition at a critical angular difference between the two preferred directions: in both flocking and spin models the transition coincides with the change in the group dynamics from Brownian to persistent collective motion. The groups undergo this transition as the number of uninformed individuals (those in the group that do not exhibit a directional preference) increases, which acts as an inverse of the temperature (noise) of the spin model. When the two informed subgroups are not equal in size, there is a tendency for the group to reach the target preferred by the larger subgroup. We find that the spin model captures effectively the essence of the collective decision-making transition and allows us to reveal a noise-dependent trade-off between the decision-making speed and the ability to achieve majority (democratic) consensus.
"Sporadic Alzheimer's disease – does it start with altered ubiquitin signaling?”
Lecture
Tuesday, October 29, 2019
Hour: 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
"Sporadic Alzheimer's disease – does it start with altered ubiquitin signaling?”
Prof. Michael H. Glickman
Department of Biology, Technion, Haifa
With our rapidly aging population, Alzheimer’s disease (AD) is often considered the plague of the 21st century. While much is known regarding the direct genetic mutations that trigger the rare familial form of the disease (FAD), molecular mechanisms driving the emergence of late-onset sporadic AD (SAD) remain elusive. A distinctively human predicament, AD is a protein-based disease characterized by toxic protein build up in the brain. The principal mechanisms for protein turnover or removal are dependent on ubiquitin. We will describe evidence that interference with ubiquitin signalling in a 3-dimentional human neuronal culture is sufficient to cause the two pathological hallmarks of AD (A plaques and neurofibrillary tangles), even in the absence of any familial mutations. By utilizing this platform, we specifically demonstrate that attenuated ubiquitin-dependent turnover leads to elevated levels of the Amyloid Precursor Protein (APP), enhanced secretion of the toxic amyloid-β42 peptide, and extra-cellular amyloid plaque build-up. Furthermore, we demonstrate that impaired ubiquitin signalling is a common feature of different human and murine models of AD, whereas overcoming this impairment is sufficient to decrease formation of A plaques and neurofibrillary tangles in an experimental model of FAD. To summarise, our work uncovers a role for ubiquitin during the early “cellular phase” of neurodegeneration that underlies emergence and progression of AD, providing hope that tweaking components of the ubiquitin-proteasome system has the potential to decrease risk for developing AD pathology, opening up new therapeutic approaches.
Neural and emotional states under social interactions
Lecture
Thursday, October 10, 2019
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Neural and emotional states under social interactions
Raviv Pryluk (PhD Thesis Defense)
Rony Paz Lab, Dept of Neurobiology, WIS
Primates live in large and complex social groups. It has been argued that this has led to evolutionary pressure on the brain and that there are networks that have been evolved to play an important role in social cognition and behaviors. Social deficits are widely known in many brain disorders such as autism and anxiety. Here we focused on two brain areas that were shown to play a crucial role in social interactions – the amygdala and the anterior-cingulate-cortex (ACC). Our goal was to understand the neural codes in these two regions and especially under social interactions:
1. Computational techniques that allow the comparison of on-going neural activity across these brain regions and species based on information theory measures was developed. We found that human neurons better utilize information capacity (efficient coding) than macaque neurons in both regions, and that ACC neurons are more efficient than amygdala neurons, in both species. In contrast, we found more overlap in the neural vocabulary and more synchronized activity (robustness coding) in monkeys in both regions, and in the amygdala of both species. Our findings demonstrate a tradeoff between robustness and efficiency across species and regions. We suggest that this tradeoff can contribute to the differential cognitive functions between species, and can underlie the complementary roles of the amygdala and the ACC. It can also contribute to the fragility underlying human psychopathologies. For more, see https://www.sciencedirect.com/science/article/pii/S0092867418316465
2. A novel electrophysiology experiment that induced real and live social interactions between humans and primates was conducted. In each daily session, we recorded neural responses in monkeys to the eye-gaze, direct or averted, of human intruders, and compared it with the responses to valence conditioning, aversive and appetitive. We found that the primate amygdala, but not the ACC, encodes eye-gaze; this coding is shared with valence coding through two mechanisms – “shared-activity” at the expectation epoch (conditioned stimulus, CS) and “shared-intensity” after the outcome (unconditioned stimulus, US). These shared mechanisms can open an indirect window for future therapy. For more, see https://www.biorxiv.org/content/10.1101/736462v1
3. We developed behavioral methods and algorithms to evaluate primates’ emotional states, using the analysis of facial expressions and a number of physiological parameters such as heart rate and respiratory rate. The primates’ emotional state evaluation will be the substrate for future studies that will investigate the neural correlates of these states.
Tonic GABAA receptor mediated conductance at cellular and network levels
Lecture
Monday, September 23, 2019
Hour: 14:00 - 15:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Tonic GABAA receptor mediated conductance at cellular and network levels
Prof. Alexey Semyanov
Head, Dept of Molecular Neurobiology, Institute of BioOrganic Chemistry, Moscow
GABAA receptors mediate two forms of signaling in the brain: phasic and tonic. Phasic signaling (e.g., IPSCs) is mediated by synaptic GABAA receptors, while tonic signaling (e.g., tonic current or tonic conductance) is mediated by extrasynaptic GABAA receptors. Tonic current is expressed in a cell-type specific manner and is mediated by heterogeneous and plastic GABAA receptors. These receptors are activated by ambient GABA that originates from vesicular and non-vesicular sources and is regulated by different GABA transporter systems.
Tonic GABAA conductance is commonly referred as tonic inhibition. We found that ambient GABA can actually excite adult hippocampal interneurons. In these cells, the GABAA reversal potential is depolarizing, making baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Because hippocampal interneurons are the key to setting the network rhythms this mechanism allows bidirectional control of network synchronization by tonic GABAA receptor-mediated signaling.
We also show that tonic GABAA conductance decreases the membrane time constant (τm) and improves the temporal fidelity of EPSP-spike coupling. Long-term potentiation (LTP) induced by different stimulation patterns is differently affected by tonic GABAA conductance.
Our findings thus point to an important role of extrasynaptic signaling mediated by GABAA receptors in brain computations.
Intracranial electrophysiology of speech perception and production
Lecture
Monday, August 12, 2019
Hour: 13:30 - 14:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Intracranial electrophysiology of speech perception and production
Dr. Adeen Flinker,Naomi Moses
NYU Langone, Dept of Neurology
For many decades, the neurobiological basis of language has been dominated by a conceptually dichotomous model in which speech perception is supported by Wernicke’s area in the temporal lobe and speech production is supported by Broca’s area in the frontal lobe. This model has been challenged by lesion and neuroimaging studies suggesting a more complex network of cortical structures supporting language. Many of the questions remaining in the field require a fine-grained temporal resolution together with spatial specificity in order to assay the dynamics of speech. Here I will introduce a series of studies employing direct electrocorticographic (ECoG) recordings in humans, illuminating the dynamics and cascade of neural events from perception to production of speech.
Cytokines as neuromodulators: How immunity affects brain function
Lecture
Thursday, June 27, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Cytokines as neuromodulators: How immunity affects brain function
Prof. Jonathan Kipnis
Center for Brain Immunology and Glia (BIG), Dept of Neuroscience University of Virginia, Charlottesville, VA
Immune cells and their derived molecules have major impact on brain function, but despite the robust influence on brain function, peripheral immune cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between immunity and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place and through which it impacts brain function. Unique sub-types of immune cells within meningeal spaces are producing certain sets of cytokines that impact specific behaviors. Three main cytokines and their neuromodulatory functions will be discussed in social, learning and risk-taking behaviors.
The Role of DOC2B in Vesicle Fusion and Asynchronous Neurotransmitter Release
Lecture
Tuesday, June 25, 2019
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
The Role of DOC2B in Vesicle Fusion and Asynchronous Neurotransmitter Release
Prof. Uri Ashery
Sagol School of Neuroscience and School of Neurobiology,
Biochemistry and Biophysics,
Life Sciences Faculty,
Tel Aviv University
DOC2B is a high-affinity Ca2+ sensor, which translocates from the cytosol to the plasma membrane (PM) upon Ca2+ elevation and regulates exocytosis by promoting priming and fusion. Its interaction with the PM depends both on calcium and on its C2 domains binding to phosphoinositides (PI(4,5)P2) at the PM. In the lecture, I will move from the level of protein structure and its targeting to PI(4,5)P2 via its effect on vesicle fusion in chromaffin cells up to its involvement in asynchronous release in neurons and its effects on neuronal network activity.
Environmental affordances and the neural representation of complex space
Lecture
Monday, June 17, 2019
Hour: 16:00 - 17:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Environmental affordances and the neural representation of complex space
Prof. Kate Jeffery
University College London
Externally and internally induced arousal states modify spontaneous and evoked synaptic activities in the mouse somatosensory cortex
Lecture
Monday, June 17, 2019
Hour: 13:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Externally and internally induced arousal states modify spontaneous and evoked synaptic activities in the mouse somatosensory cortex
Akiva Rapaport (PhD Thesis Defense)
Ilan Lampl Lab, Dept of Neurobiology, WIS
Behavioral states, such as arousal and attention are defined by a set of psychological and physiological variables. They have profound effects on sensation, perception, learning, and cognition. In the brain, global states are characterized by distinct cortical and hippocampal EEG patterns. These changes that are clearly observed in the local field potential (LFP) are also evident in network and cellular dynamics. At the population level, the more active states are manifested as asynchronous neuronal firing between neighboring cells. At the cellular level, the membrane potential during active states is characterized by a continuous depolarized state, high synaptic ac! tivity, reduced variance and reduced membrane potential correlations between cells. In recent years it has been demonstrated in rodents that pupil size is a robust indicator of a range of neural activity from neuromodulator release to cortical neuronal membrane potential.
There has been some debate in the field regarding to what extent the effects of locomotion on cortical dynamics are due to arousal and what can be attributed to locomotion. Furthermore, in some studies cortical dynamics were evaluated while the animals transitioned spontaneously between states and in others, states of arousal were externally induced. Additionally, different effects have been reported in the auditory and visual cortex. Therefore, we wanted to more finely differentiate between different states and evaluate the effect of state on the somatosensory cortex.
To accomplish this we conducted intracellular recordings in the barrel cortex as well as extracellular LFP recordings in Layer IV of the barrel cortex in awake head fixed mice. We monitored pupil size as an indicator for state of arousal as well as tracking locomotion.
We found that there is a significant correlation between membrane potential of cells in barrel cortex and pupil size. Neurons were significantly more depolarized as the animal was in a greater state of arousal. This change was not affected by the mode of inducement of arousal, be it a spontaneous transition into a state of arousal or one externally induced. However, the effect was abolished by the occurrence of locomotion.
We also found that responses to sensory stimuli are increased during a state of arousal but not in a state of hyper-arousal. Inducing the state externally minimized this effect and if the animal is locomoting then the increase in sensory responses is abolished.
We further found that when the animal is in a greater state of arousal there is less synchronization as indicated by the decrease in correlation between membrane potential and LFP. Even more startlingly, we found that the polarity of the cross-correlation was reversed during hyperarousal. This would strongly suggest a reorganization of the laminar network across different states.
Pages
2019
All events, 2019
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