Jessica Cardin

Last updated
Jessica Cardin
NationalityAmerican
Alma materCornell University, University of Pennsylvania
Known forCombined optogenetics and electrophysiology, behavioral state dependency of cortical neural circuit function
Scientific career
FieldsNeuroscience
InstitutionsYale School of Medicine

Jessica Cardin is an American neuroscientist who is an associate professor of neuroscience at Yale University School of Medicine. Cardin's lab studies local circuits within the primary visual cortex to understand how cellular and synaptic interactions flexibly adapt to different behavioral states and contexts to give rise to visual perceptions and drive motivated behaviors. Cardin's lab applies their knowledge of adaptive cortical circuit regulation to probe how circuit dysfunction manifests in disease models.

Contents

Early life and education

In grade nine, she conducted an experiment in her house, using mice as a model organism to probe sex based differences in learning. [1] Cardin pursued her undergraduate degree at Cornell University in Ithaca, New York where she majored in biological sciences and started conducting research in a real laboratory, instead of her own home. [2] At Cornell, Cardin joined the lab of Timothy J. DeVoogd, where she studied learning in songbirds and mapped out the morphology and anatomy of the high vocal center (HVC) in female canaries. [3] Her undergraduate research led to a publication in Brain Research where she helped to adapt a technique to morphologically define specific projection pathways to the high vocal center (HVC). [3] They describe their discovery of neurons projecting to AreaX that receive direct auditory input to support the function of the HVC in song learning. [3]

After graduating with a B.A. from Cornell in 1997, Cardin pursued her graduate studies in neuroscience at the University of Pennsylvania. [4] Once at UPenn, Cardin rotated in the lab of Ted Abel, a new faculty member at the time, studying the molecular basis of memory storage. [5] During her rotation, Cardin helped Abel write a review paper exploring the memory suppression both in invertebrates and vertebrates. [5] In 2000, Cardin joined the lab of Marc Schmidt where she returned to the model organism used in her undergraduate degree, songbirds, but this time she probed the behavioral state dependency of auditory processing in songbird neural circuits. [4]

Cardin completed her PhD training in 2004 and stayed in Philadelphia to complete her postdoctoral fellowship in the Department of Neuroscience at the UPenn Medical School. [6] Working under the mentorship of Diego Contreras, Cardin delved into electrophysiology, where she was able to record neural activity at single cell resolution in the visual cortex of cats to probe the dynamics of visual cortex computations. [1]  She completed her postdoctoral training in 2009, but from 2007 to 2009, Cardin trained simultaneously under Christopher I. Moore at the Massachusetts Institute of Technology within the McGovern Institute where she began to pioneer new applications of optogenetics to probing and recording from neural circuits. [4]

Research

During her graduate studies, Cardin explored the variability in sensory processing across brain states, such as during sedation, wakefulness, and high arousal. [7] She found that behavioral states drastically influence the neural firing patterns of auditory neurons. [7] While songbirds are asleep, the neurons in the HVC increase in firing, with selectivity towards the birds own song, while when songbirds are awake, there is much more variability in firing and there is no longer selectivity towards the bird's own song. [7] They further found that arousal suppressed the responsiveness of the HVC which suggests that other mechanisms must be at play to enhance auditory responsiveness in awake states. [7]

After discovering that the HVC is modulated according to behavioral state, Cardin then found that an upstream brain area, called the nucleus interfacialis (NiF) is also modulated by behavioral state. [8] By pharmacologically inhibiting and exciting the NiF, Cardin found that the NiF is the primary integration site of behavioral state information and it relays this information to the HVC to drive its responsiveness to behavioral state. [8] Following this study, Cardin showed that specifically the noradrenergic neurons in the NiF are what mediate NiF neuron responsiveness to brain state. [9]  Overall, Cardin's findings in graduate school highlight the noradrenergic neurons in the NiF as the critical integrators of brain state to relay state information during vocal learning in songbirds. [9]

In her postdoctoral work, Cardin explored gamma oscillations in the primary visual cortex of cats. [10] She explored both simple and complex cells in the primary visual cortex and found that, while they both burst at gamma frequencies, only simple cells show a selective stimulus feature-dependent response to visual stimulation. Since rhythmic synaptic input drives visually evoked activity in both simple and complex fast rhythmic bursting cells of the visual cortex, Cardin proposes that these cells may distribute stimulus driven gamma oscillations throughout the neocortex. [10]

Following this paper, Cardin and her team validated the existence of gain modulation in the primary visual cortex. [11] Gain modulation is a neural phenomenon in which response amplitude is modified without changing selectivity. [11] Cardin and her team performed intracellular recordings in the cat primary visual cortex and found that gain modulation is determined instantaneously by the rapidly changing sensory context and the dynamics of synaptic activation. [11]

After focusing on the visual system, Cardin conducted a brief postdoctoral position at M.I.T. where she learned optogenetics and employed the technology in novel ways to further the findings she had made previously in her postdoc at UPenn. Cardin helped elucidate experimental support for the fast-spiking gamma hypothesis. [12] They found that fast-spiking interneurons had amplified gamma oscillations when driven at frequencies between 8 and 200 Hz through optogenetic manipulation. [12] They further showed this was not the case for pyramidal neurons, whose neural activity is amplified at low frequencies. [12]  Overall, they showed that network activity states can be driven in vivo using cell-type specific optogenetics. [12] Following this paper, Cardin and a team of researchers developed a protocol to both stimulate neurons optogenetically and record evoked activity in vivo using electrophysiological preparations. [13] Their technology enabled researchers to ask questions about the roles of specific neural populations in the brain at much greater specificity than ever before. [13]

Career

In 2010, Cardin was recruited to Yale University School of Medicine and became an assistant professor in the Department of Neurobiology. [6] In 2012, she became a member of the Kavli Institute for Neuroscience at Yale. [6] Cardin's lab probes cortical neural circuits to understand how cellular and synaptic interactions flexibly adapt to different behavioral states and environmental contexts to give rise to visual perceptions and drive motivated behaviors. [14] Cardin's lab further applies their knowledge of adaptive cortical circuit regulation to probe how circuit dysfunction manifests in disease models. [14] In addition to her roles in the lab, Cardin is on the Brain Science Mindscope Advisory Council as an Allen Institute Advisor [15]  and has been integrally involved in the organization and planning of the COSYNE Conference since 2009. [14]

Functional Flexibility in Neural Circuits

Cardin is interested in understanding how the brain can function without needing more neurons, specialized to specific behavioral states. [14] Because neurons are able to so quickly respond and adapt to different environments and arousal states, Cardin and her team explored the neural activity governing transitions between distinct waking states. [16] Heightened arousal states, compared to quiescent states, suppressed spontaneous neural firing and increased the signal to noise ratio of visual responses. [16] Their findings pointed to the distinct behavior of neurons in different states and that the malleable activity patterns in cortical circuits are driven by both arousal state and locomotion in different ways. [16]

Following this study, Cardin and her team used in vivo calcium imaging to look at three distinct populations of projection neurons in the visual cortex to determine if they encoded and transferred unique information to downstream structures about the visual environment. [17] They found that specific projection populations process and route visual information to downstream targets in functionally different ways to inform behavior. [17]

Cardin and her team recently[ when? ] probed the role of vasoactive intestinal peptide (VIP) expressing interneurons in cortical neural circuit regulation. [18] By removing a critical signalling receptor, ErbB4, from VIP neurons, Cardin and her team saw deficits in sensory processing and dysregulation of cortical state dependence they had shown was important to cortical function in earlier experiments. [18] Interestingly, the dysregulation in neural circuit function manifested in adolescence, even though ErbB4 was removed in development, suggesting that developmental aberrations in cortical circuit development might not present until later in life, mimicking the prognosis of many brain-related diseases and shedding insight into their possibly developmental origins. [18]

Awards and honors

Select publications

Related Research Articles

The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

<span class="mw-page-title-main">Claustrum</span> Structure in the brain

The claustrum is a thin, bilateral collection of neurons and supporting glial cells, that connects to cortical and subcortical regions of the brain. It is located between the insula laterally and the putamen medially, separated by the extreme and external capsules respectively. The blood supply to the claustrum is fulfilled via the middle cerebral artery. It is considered to be the most densely connected structure in the brain, allowing for integration of various cortical inputs into one experience rather than singular events. The claustrum is difficult to study given the limited number of individuals with claustral lesions and the poor resolution of neuroimaging.

<span class="mw-page-title-main">Interneuron</span> Neurons that are not motor or sensory

Interneurons are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. Interneurons are the central nodes of neural circuits, enabling communication between sensory or motor neurons and the central nervous system (CNS). They play vital roles in reflexes, neuronal oscillations, and neurogenesis in the adult mammalian brain.

<span class="mw-page-title-main">Reticular formation</span> Spinal trigeminal nucleus

The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts.

A gamma wave or gamma rhythm is a pattern of neural oscillation in humans with a frequency between 25 and 140 Hz, the 40 Hz point being of particular interest. Gamma rhythms are correlated with large scale brain network activity and cognitive phenomena such as working memory, attention, and perceptual grouping, and can be increased in amplitude via meditation or neurostimulation. Altered gamma activity has been observed in many mood and cognitive disorders such as Alzheimer's disease, epilepsy, and schizophrenia.

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

<span class="mw-page-title-main">Thalamocortical radiations</span> Neural pathways between the thalamus and cerebral cortex

In neuroanatomy, thalamocortical radiations are the fibers between the thalamus and the cerebral cortex.

<span class="mw-page-title-main">Neural oscillation</span> Brainwaves, repetitive patterns of neural activity in the central nervous system

Neural oscillations, or brainwaves, are rhythmic or repetitive patterns of neural activity in the central nervous system. Neural tissue can generate oscillatory activity in many ways, driven either by mechanisms within individual neurons or by interactions between neurons. In individual neurons, oscillations can appear either as oscillations in membrane potential or as rhythmic patterns of action potentials, which then produce oscillatory activation of post-synaptic neurons. At the level of neural ensembles, synchronized activity of large numbers of neurons can give rise to macroscopic oscillations, which can be observed in an electroencephalogram. Oscillatory activity in groups of neurons generally arises from feedback connections between the neurons that result in the synchronization of their firing patterns. The interaction between neurons can give rise to oscillations at a different frequency than the firing frequency of individual neurons. A well-known example of macroscopic neural oscillations is alpha activity.

<span class="mw-page-title-main">Synaptic gating</span>

Synaptic gating is the ability of neural circuits to gate inputs by either suppressing or facilitating specific synaptic activity. Selective inhibition of certain synapses has been studied thoroughly, and recent studies have supported the existence of permissively gated synaptic transmission. In general, synaptic gating involves a mechanism of central control over neuronal output. It includes a sort of gatekeeper neuron, which has the ability to influence transmission of information to selected targets independently of the parts of the synapse upon which it exerts its action.

Recurrent thalamo-cortical resonance is an observed phenomenon of oscillatory neural activity between the thalamus and various cortical regions of the brain. It is proposed by Rodolfo Llinas and others as a theory for the integration of sensory information into the whole of perception in the brain. Thalamocortical oscillation is proposed to be a mechanism of synchronization between different cortical regions of the brain, a process known as temporal binding. This is possible through the existence of thalamocortical networks, groupings of thalamic and cortical cells that exhibit oscillatory properties.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient.

<span class="mw-page-title-main">Neural correlates of consciousness</span> Neuronal events sufficient for a specific conscious percep

The neural correlates of consciousness (NCC) refer to the relationships between mental states and neural states and constitute the minimal set of neuronal events and mechanisms sufficient for a specific conscious percept. Neuroscientists use empirical approaches to discover neural correlates of subjective phenomena; that is, neural changes which necessarily and regularly correlate with a specific experience. The set should be minimal because, under the materialist assumption that the brain is sufficient to give rise to any given conscious experience, the question is which of its components is necessary to produce it.

Christopher I. Moore is a neuroscientist at Brown University.

<span class="mw-page-title-main">Karl Deisseroth</span> American optogeneticist

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

Lisa Gunaydin is an American neuroscientist and assistant professor at the Weill Institute for Neurosciences at the University of California San Francisco. Gunaydin helped discover optogenetics in the lab of Karl Deisseroth and now uses this technique in combination with neural and behavioral recordings to probe the neural circuits underlying emotional behaviors.

Ilana B. Witten is an American neuroscientist and professor of psychology and neuroscience at Princeton University. Witten studies the mesolimbic pathway, with a focus on the striatal neural circuit mechanisms driving reward learning and decision making.

<span class="mw-page-title-main">Laura Busse</span> German neuroscientist

Laura Busse is a German neuroscientist and professor of Systemic Neuroscience within the Division of Neurobiology at the Ludwig Maximilian University of Munich. Busse's lab studies context-dependent visual processing in mouse models by performing large scale in vivo electrophysiological recordings in the thalamic and cortical circuits of awake and behaving mice.

<span class="mw-page-title-main">Brain cell</span> Functional tissue of the brain

Brain cells make up the functional tissue of the brain. The rest of the brain tissue is structural or connective called the stroma which includes blood vessels. The two main types of cells in the brain are neurons, also known as nerve cells, and glial cells also known as neuroglia.

<span class="mw-page-title-main">Eberhard Fetz</span> American neuroscientist, academic and researcher

Eberhard Erich Fetz is an American neuroscientist, academic and researcher. He is a Professor of Physiology and Biophysics and DXARTS at the University of Washington.

Sonja Hofer is a German neuroscientist studying the neural basis of sensory perception and sensory-guided decision-making at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour. Her research focuses on how the brain processes visual information, how neural networks are shaped by experience and learning, and how they integrate visual signals with other information in order to interpret the outside world and guide behaviour. She received her undergraduate degree from the Technical University of Munich, her PhD at the Max Planck Institute of Neurobiology in Martinsried, Germany, and completed a post doctorate at the University College London. After holding an Assistant Professorship at the Biozentrum University of Basel in Switzerland for five years, she now is a group leader and Professor at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour since 2018.

References

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  17. 1 2 Lur, Gyorgy; Vinck, Martin A.; Tang, Lan; Cardin, Jessica A.; Higley, Michael J. (2016-03-22). "Projection-Specific Visual Feature Encoding by Layer 5 Cortical Subnetworks". Cell Reports. 14 (11): 2538–2545. doi: 10.1016/j.celrep.2016.02.050 . ISSN   2211-1247. PMC   4805451 . PMID   26972011.
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