Hillel Adesnik

Associate Professor, Affiliated of Cell Biology, Development and Physiology

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Research Interests

Our brain is responsible for all our perceptions, thoughts and actions. Despite the incredible array of processes the brain performs - from memory to emotion - its elementary units of function are the nerve cell and the synaptic junction. How is it that a collection of neurons and their synapses gives rise to all of animal and human behavior?

In mammals and especially in humans, the cerebral cortex is an area of the brain that is crucially involved in nearly all cognitive functions. Individual neurons in the cortex can make over 10,000 connections with other brain cells. The precise pattern of connections between a local group of neurons in the cortex gives rises to its elementary unit of computation - the cortical microcircuit.

The goal of our laboratory is to reveal the neural basis of perception. More specifically, we want to understand exactly how cortical microcircuits process sensory information to drive behavior. While decades of research have carefully outlined how individual neurons extract specific features from the sensory environment, the cellular and synaptic mechanisms that permit ensembles of cortical neurons to actually process sensory information and generate perceptions are largely unknown.

Addressing this fundamental question of modern neuroscience requires working at both the cellular and system-wide level to assess how populations of neurons cooperate to encode information, generate perceptions, and execute behavioral decisions. Towards this end, we monitor and and then manipulate specific subsets of genetically identified neurons in awake behaving mice to quantitatively determine their contribution to sensory processing and behavior. By turning neurons 'on' and 'off' using optogenetic and pharmacogenetic approaches, we can identify groups of cortical neurons that are both necessary and sufficient for specific neural computations. By complementing our in vivo work with detailed analysis of synaptic connectivity and network dynamics in vitro, we hope to arrive at a more complete understanding for how neural circuits in our brain support sensation, cognition, and action. Our lab is also developing a suite of novel optical and genetic approaches to manipulate neural circuits in the intact brain and at far greater resolution than is possible with current techniques. These new tecniques will allow us to address fundamental questions about sensory computation and perception that have as yet eluded investigation.

Current Projects

There are three major aims of our research. Our first goal is to understand the role of horizontal and vertical connections across each of the six major cortical layers in computing the size, shape, and texture of sensory objects. Horizontal connections that connect cortical columns are likely to play a critical role in these processes by providing a context for sensory stimuli in space. We take advantage of the mouse 'barrel' cortex in which each cortical column represents one whisker on the face. Using multi-electrode array recordings, two photon imaging, and in vivo whole cell voltage clamp recordings in the barrel cortex of awake, actively whisking mice we are dissecting the cortical circuits responsible for encoding and decoding tactile stimuli.

The second goal of the lab is to develop new high-speed and spatially precise optical approaches to manipulate neural activity at the level of single neurons in the intact brains of awake, behaving animals to decipher the neural code that underlies sensory perception. By combining non-linear optics with optogenetics we aim to control the activity of hundreds to thousands of neurons at single cell resolution, providing the key tool to understand how patterns of action potentials in space and time represent the external world.

Our third goal is to understand how global activity across mutliple sensory, motor and associational cortical areas, synthesizes specfic perceptions and selects the appropriate behavioral response to a given set of environmental conditions. We combine whole brain imaging approaches with targeted electrophysiology to reveal how communication within and across cortical areas cooperate to generate specific percepts.

Our hope is that by understanding how the brain generates perceptions at the level of synapses and circuits we will not only come to a much deeper appreciation for the biological mechanisms underlying brain function, but also reveal new avenues to treat neurological disease such as autism, schizophrenia, epilepsy, and movement disorders.

Selected Publications

Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)  Yi Xue, Laura Waller, Hillel Adesnik, Nicolas Pégard eLife in press

High performance microbial opsins for spatially and temporally precise perturbations of large neuronal networks Savitha Sridharan, Marta Gajowa, Mora B. Ogando, Uday Jagadisan, Lamiae Abdeladim, Masato Sadahiro, Hayley Bounds, William D. Hendricks, Ian Tayler, Karthika Gopakumar, Ian Antón Oldenburg, Stephen G. Brohawn, Hillel Adesnik Neuron in press

Synthesis of higher order feature codes through stimulus-specific supra-linear summation Evan H. Lyall, Daniel P. Mossing, Scott R. Pluta, Amir Dudai, Hillel Adesnik Elife. 2021 Nov 1;10:e62687. doi: 10.7554/eLife.62687.

Spatial integration during active tactile sensation drives orientation perception. Brown J, Oldenburg IA, Telian GI, Griffin S, Voges M, Jain V, Adesnik H. Neuron. 2021 Mar 30:S0896-6273(21)00190-2. doi: 10.1016/j.neuron.2021.03.020.

Ultrasound activates mechanosensitive TRAAK K+ channels through the lipid membrane. Sorum B, Rietmeijer RA, Gopakumar K, Adesnik H, Brohawn SG.Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2006980118. doi: 10.1073/pnas.2006980118.

Precision multidimensional neural population code recovered from single intracellular recordings. Johnson JK, Geng S, Hoffman MW, Adesnik H, Wessel R.Sci Rep. 2020 Sep 29;10(1):15997. doi: 10.1038/s41598-020-72936-1.

Complementary networks of cortical somatostatin interneurons enforce layer specific control. Naka A, Veit J, Shababo B, Chance RK, Risso D, Stafford D, Snyder B, Egladyous A, Chu D, Sridharan S, Mossing DP, Paninski L, Ngai J, Adesnik H. Elife. 2019 Mar 18;8. pii: e43696. doi: 10.7554/eLife.43696.

Superficial Layers Suppress the Deep Layers to Fine-tune Cortical Coding. Pluta SR, Telian GI, Naka A, Adesnik H.J Neurosci. 2019 Mar 13;39(11):2052-2064. doi: 10.1523/JNEUROSCI.1459-18.2018. Epub 2019 Jan 16.

Cracking the Function of Layers in the Sensory Cortex. Adesnik H, Naka A Neuron. 2018 Dec 5;100(5):1028-1043. doi: 10.1016/j.neuron.2018.10.032. Review.

Precise multimodal optical control of neural ensemble activity. Mardinly AR, Oldenburg IA, Pégard NC, Sridharan S, Lyall EH, Chesnov K, Brohawn SG, Waller L, Adesnik H. Nat Neurosci. 2018 Jun;21(6):881-893. doi: 10.1038/s41593-018-0139-8

A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex. Hakim RH, Shamardani K, Adesnik H. eLife. 2018 Feb 26;7. doi: 10.7554/eLife.28569.

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex. Adesnik H. J Physiology 2018 Jan 5. doi: 10.1113/JP274986.

Three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT). Pegard NC, Mardinly AR, Oldenburg IA, Sridharan S, Walller L, Adesnik H. Nature communications 2017 Oct 31;8(1):1228.

Synaptic Mechanisms of Feature Coding in the Visual Cortex of Awake Mice. Adesnik H. Neuron 2017 Aug 30;95(5):1147-1159

Cortical gamma band synchronization through somatostatin interneurons. Veit J, Hakim R, Jadi MP, Sejnowski TJ, Adesnik H Nature Neuroscience 2017 May 8. Jul;20(7):951-959.

Surround Integration Organizes a Spatial Map during Active Sensation. Pluta SR, Lyall EH, Telian GI, Ryapolova-Webb E, Adesnik H Neuron 2017 Jun 21;94(6):1220-1233.e5

Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons. Mardinly AR, Spiegel I, Patrizi A, Centofante E, Bazinet JE, Tzeng CP, Mandel-Brehm C, Harmin DA, Adesnik H, Fagiolini M, Greenberg ME. Nature. 2016 Mar 17;531(7594):371-5

Compressive light-field microscopy for 3D neural activity recording Pégard NC, Liu HY, Antipa N, Gerlock M, Adesnik H, Waller L. Optica 2016 3 (5), 517-52

Bayesian methods for event analysis of intracellular currents. Josh Merel*, Ben Shababo*, Alex Naka, Hillel Adesnik, Liam Paninski. Journal of Neuroscience Methods 269, 201610.1016/j.jneumeth.2016.05.015

Inhibitory Circuits in Cortical Layer 5. Naka A, Adesnik H. Front Neural Circuits. 2016 May 6;10:35. doi: 10.3389/fncir.2016.0003

A direct translaminar inhibitory circuit tunes cortical output. Pluta S, Naka A, Veit J, Telian G, Hakim R, Taylor D, Yao L, Adesnik H. Nature Neuroscience. 2015 2015 Nov;18(11):1631-40

A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABA(A) Receptors and Synaptic Inhibition. Lin WC, Tsai MC, Davenport C, Smith C, Veit J, Wilson N, Adesnik H, Kramer RH. Neuron, 2015 Dec 2;88(5):879-91.

Optogenetic pharmacology for control of native neuronal signaling proteins. Kramer RH, Mourot A, Adesnik H. Nature Neuroscience 2013 Jul;16(7):816-23.

A neural circuit for spatial summation in visual cortex. Adesnik H, Bruns W, Taniguchi H, Huang ZJ, Scanziani M. Nature. 2012 Oct 11;490(7419):226-31.

Gain control by layer six in cortical circuits of vision. Olsen SR, Bortone DS, Adesnik H, Scanziani M. Nature. 2012 Feb 22;483(7387):47-52

Lateral competition for cortical space by layer-specific horizontal circuits. Adesnik H, Scanziani M. Nature. 2010 Apr 22;464(7292):1155-60.

NMDA receptors inhibit synapse unsilencing during brain development. Adesnik H, Li G, During MJ, Pleasure SJ, Nicoll RA. PNAS. 2008 Apr 8;105(14):5597-602.

Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M. Science. 2006 Sep 22;313(5794):1792-5.

Photoinactivation of native AMPA receptors reveals their real-time trafficking. Adesnik H, Nicoll RA, England PM. Neuron. 2005 Dec 22;48(6):977-85.

Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Tomita S, Adesnik H, Sekiguchi M, Zhang W, Wada K, Howe JR, Nicoll RA, Bredt DS. Nature. 2005 Jun 23;435(7045):1052-8. Epub 2005 Apr 27.

Last Updated 2022-01-20