Attila Losonczy, MD, PhD
- Associate Professor of Neuroscience
A fundamental capacity of the mammalian cerebral cortex is to process information in a form conducive to encoding, storage and retrieval of memories. A general organizational principle of cortical mnemonic circuits states that these steps all require a precisely orchestrated spatio-temporal interaction among a large number of relatively uniform excitatory and a numerically fewer but richly diverse population of inhibitory and neuromodulatory circuit elements. However, a mechanistic understanding of how these circuit motifs interact during elementary steps of memory processing is lacking. Our general hypothesis is that single neurons perform complex computations by exploiting their multilayered and compartmentalized dendritic arborization. Specifically, we hypothesize that, (1) neuronal dendritic arbor constitutes a backbone for both compartmentalized input integration and plasticity, and (2) dynamic interactions between synaptic and intrinsic forms of neuronal plasticity can expand neuron’s capability to detect, store and recall various features of information.
To test these predictions, we use a variety of techniques: direct electrophysiological recordings from various compartments of neurons, simultaneous patch-clamp recordings from multiple neurons, together with two-photon imaging/photoactivation and optogenetics.
A major focus of our lab will be to understand how dynamic spatio-temporal interactions among excitatory, inhibitory and neuromodulatory inputs in different subcellular domains fundamentally enhance information processing and storage capabilities of single and small networks of neurons in the hippocampal circuit
Another aspect of our work will focus on testing the prediction that intrinsic and synaptic forms of neuronal plasticity bidirectionally interact within dendritic compartments. We also aim to reveal exact mechanisms how these different forms of neuronal plasticity are affected by inhibition and neuromodulation.
The long-term goal of our laboratory is to establish causal links between single cell computations and behavior.
- Neurobiology of Learning and Memory
- Synapses and Circuits
- Systems and Circuits
1. Royer S, Zemelman BV, Losonczy A, BuzsÃ¡ki G, and Magee JC (2010) Optoelectronic neural interface (ONI): light-assisted perturbation of silicon probe-monitored local circuits in the behaving animal. European Journal of Neuroscience, 31: 2279-2291
2. Losonczy A, Zemelman BV, Vaziri A, and Magee JC (2010) Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons. Nature Neuroscience, 13: 967-972
3. Lovett-Barron M, Turi GF, Kaifosh P, Lee PH, Bolze F, Sun XH, Nicoud JF, Zemelman BV, Sternson SM, and Losonczy A* (2012) Regulation of neuronal input output transformation by tunable dendritic inhibition. Nature Neuroscience, 15: 423-430
Oren I, and Kullmann D (2012) New and Views, Nature Neuroscience, 15: 344-345.Cover illustration
4. Royer S, Zemelman BV, Losonczy A, Kim J, Chance F, Magee JC, and BuzsÃ¡ki G, (2012). Control of timing, rate and firing patterns of hippocampal place cells by dendritic and perisomatic inhibition. Nature Neuroscience, 15: 769-775
5. Kaifosh P, Lovett-Barron M, Turi GF, Reardon, TR, and Losonczy A* (2013). Septo-hippocampal GABAergic signaling across multiple modalities in awake mouse. Nature Neuroscience, 16: 1182-1184
6. Lovett-Barron M, Kaifosh P, Kheirbek MA, Danielson N, Zaremba JD, Reardon TR, Turi GF, Hen R, Zemelman BV, and Losonczy A* (2014). Dendritic inhibition in the hippocampus supports fear learning. Science, 21: 857-63
7. Lee SH, Marchionni I, Bezaire M, Varga C, Danielson N, Lovett-Barron M, Losonczy A, and Soltesz, I. (2014). Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells. Neuron, 82:1129-1144
8. Denny CA, Kheirbek MA, Alba EL, Tanaka KF, Brachman RA, Laughman KB, Tomm NK, Turi GF, Losonczy A, and Hen R (2014). Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron, 83:189-201
9. Kaifosh P, Zaremba J, Danielson N, and Losonczy A* (2014) SIMA: Python software for analysis of dynamic fluorescence imaging data. Frontiers in Neuroinformatics 8:80
10. Turi GF, Wittmann G, Lechan MR, and Losonczy A* (2015) Ambient GABA modulates septo-hippocampal inhibitory terminals via presynaptic GABAB receptors. Neuropharmacology, 88:55-62
11. Basu J, Zaremba JD, Cheung SK, Hitti FL, Zemelman BV, Losonczy A, and Siegelbaum SA (2016). Gating hippocampal activity, plasticity and memory by entorhinal cortex long-range inhibition. Science, 351:(6269): aaa5694. doi: 10.1126/science.aaa5694
12. Reardon, TR, Murray AJ, Turi GF, Wirblich C, Croce K, Schnell MJ, Jessell TM, and Losonczy A* (2016). Rabies virus CVS-N2cΔG strain enhances synaptic transfer, neuronal viability and circuit analysis. Neuron, 89(4): 711-24
13. Danielson N, Zaremba JD, Kaifosh P, Lovett-Barron M, Tsai J, Denny CA, Balough ME, Cloidt MA, Drew JD, Hen R, Losonczy A*, and Kheirbek MA. (2016) Distinct contribution of adult-born hippocampal granule cells to context encoding. Neuron, 90(1): 101-112
Ramsaran, AI and Frankland PW The Young and the Promiscuous, Preview, Neuron, 90(1) 6-8
14. Kaifosh P, and Losonczy A*. (2016) Mnemonic functions for nonlinear integration of laminar inputs by hippocampal pyramidal cells. Neuron, 90(3) 622-634
15. Danielson N, Zaremba J, Kaifosh P, Bowler J, Ladow, M, and Losonczy A*. Sublayer-specific coding dynamics during spatial navigation and learning in hippocampal area CA1. (in press), Neuron