Autistic Disorder; Cerebral Cortex; Electrophysiology; Epilepsy; Interneurons; Neurobiology; Neurosciences; Schizophrenia
Neurocognition, Neurocomputation, and Neurogenetics, Division of
I am interested in how neurons in the brain communicate with each other, and how that communication leads to perception and behavior. We study how the brain represents and interprets what the eyes see, and how changes in the pattern of brain activity can change what is perceived.
Specialized Terms: Neuroscience; Cortex; Inhibitory interneuron; Oscillation; Electrophysiology; Vision; Schizophrenia; Epilepsy; Intracellular; Network
Extensive Research Description
The cortex is made up of
interconnected networks containing many different classes of neurons, whose
roles in both normal brain activity and disease are poorly understood. Each neuron contributes to activity in
the surrounding local network and receives a constant barrage of network
synaptic input in return. The
Cardin lab investigates this dynamic and bidirectional relationship between
neuron and network at multiple levels, including cellular and synaptic mechanisms,
network interactions, and behavior.
We use a variety of techniques in rodent visual cortex, including
intracellular and extracellular recordings in vivo, chronic recordings in awake behaving animals, and
optogenetic manipulations of neural activity. A main goal of work in the laboratory is to identify and
understand synaptic interactions between excitatory and inhibitory neurons
during sensory processing. One ongoing focus is the cellular mechanisms
of visual gain control and how gain modulation regulates visual perception. A second focus is to understand the
flow of signals between cortical layers and how that process is affected by
recruitment of local inhibitory interneurons. We are also interested in how interactions between different
classes of neurons change in disease states such as epilepsy and schizophrenia.
One of the most fundamental elements of brain function is a reciprocal interaction between excitatory and inhibitory neurons. A major focus in the lab is to understand how these populations of neurons regulate each other and contribute to information processing. To explore this issue, we use intracellular and extracellular recordings, along with molecular genetics techniques. Using cell type-specific expression of optogenetic tools, such as light-activated channels (Channelrhodopsin and Halorhodopsin), we can control the firing of specific populations of excitatory and inhibitory neurons and test their impact on their synaptic targets. One project in the lab is focused on using these combined techniques to map out circuit dynamics in visual cortex in vivo.
A second project is using combined optogenetics and chronic tetrode recordings in awake behaving animals. We are recording patterns of visually evoked activity during awake visual behavior and testing the impact of changing inhibitory or excitatory activity on visual perception.
A third focus is to explore the cellular mechanisms of gain control in the brain. Gain is the amplification of inputs into outputs, and can be thought of as a 'volume control' for neurons. Gain modulation allows neurons to scale their output to any range of incoming inputs. This process is well documented across the brain, but very little is known about the underlying cellular mechanisms. We are exploring the role of synchrony between neurons as a mechanism for gain control in vivo.
In addition to exploring neural dynamics in the healthy brain, we are also interested in the mechanisms of neural dysregulation during disease. Using animal models, we are studying the roles that different populations of inhibitory interneurons may play in schizophrenia. We are also studying the initiation of epilepsy and how it may be controlled with new techniques for regulating neural activity.
- Cardin, J.A. Dissecting local circuits in vivo: Integrated optogenetic and electrophysiology approaches for exploring inhibitory regulation of cortical activity. J Physiol Paris 2011, doi:10.1016/j.jphysparis.2011.09.005
- Cardin JA, Contreras D, and Palmer LA. Cellular mechanisms of temporal sensitivity in visual cortex neurons. J Neurosci In press, 2010.
- Cardin JA, Carlén EM, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, and Moore CI. Targeted optogenetic stimulation and recording of neurons in vivo using cell type-specific expression of Channelrhodopsin-2. Nature Protocols 5:247-254, 2010.
- Cardin JA, Carlén EM, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, and Moore CI. Activation of fast-spiking interneurons induces gamma oscillations and shapes sensory transmission. Nature 459:663-7, 2009.
- Cardin JA, Palmer LA, and Contreras D. Cellular mechanisms underlying stimulus-dependent gain modulation in primary visual cortex neurons Neuron 59:150-160, 2008.
- Cardin JA, Palmer LA, and Contreras D. Stimulus feature selectivity in excitatory and inhibitory neurons in primary visual cortex. J Neurosci 27:10333-44, 2007.
- Vinck, M., Batista-Brito, R., Knoblich, U., Cardin, J.A. Arousal and locomotion make distinct contributions to cortical activity patterns and visual encoding. Neuron 2015, 86,740-54.
- Furman F., Zhan Q., Lerner B., Motelow J., Meng J., Ma C., Buchanan G., Witten I.B., Deisseroth K., Cardin J.A., and Blumenfeld H. Optogenetic Stimulation of Cholinergic Brainstem Neurons During Focal Limbic Seizures: Effects on Cortical Physiology. Epilepsia 2015.
- Lur, G., Vinck M., Tang, L., Cardin J.A.*, and Higley M.J.* Projection-specific visual feature encoding by layer 5 cortical subnetworks. Cell Reports 2016, 14:2538-45.