@article {49175, title = {Elucidating neuronal mechanisms using intracellular recordings during behavior.}, journal = {Trends in Neurosciences}, volume = {41}, year = {2018}, month = {2018 Apr 20}, pages = {385-403}, abstract = {

Intracellular recording allows measurement and perturbation of the membrane potential of identified neurons with sub-millisecond and sub-millivolt precision. This gives intracellular recordings a unique capacity to provide rich information about individual cells (e.g., high-resolution characterization of inputs, outputs, excitability, and structure). Hence, such recordings can elucidate the mechanisms that underlie fundamental phenomena, such as brain state, sparse coding, gating, gain modulation, and learning. Technical developments have increased the range of behaviors during which intracellular recording methods can be employed, such as in freely moving animals and head-fixed animals actively performing tasks, including in virtual environments. Such advances, and the combination of intracellular recordings with genetic and imaging techniques, have enabled investigation of the mechanisms that underlie neural computations during natural and trained behaviors.

}, issn = {1878-108X}, doi = {10.1016/j.tins.2018.03.014}, author = {Lee, Albert K and Brecht, Michael} } @article {45041, title = {Whole-cell patch-clamp recordings in freely moving animals.}, journal = {Methods in Molecular Biology}, volume = {1183}, year = {2014}, month = {2014 Jun 20}, pages = {263-76}, abstract = {

The patch-clamp technique and the whole-cell measurements derived from it have greatly advanced our understanding of the coding properties of individual neurons by allowing for a detailed analysis of their excitatory/inhibitory synaptic inputs, intrinsic electrical properties, and morphology. Because such measurements require a high level of mechanical stability they have for a long time been limited to in vitro and anesthetized preparations. Recently, however, a considerable amount of effort has been devoted to extending these techniques to awake restrained/head-fixed preparations allowing for the study of the input-output functions of neurons during behavior. In this chapter we describe a technique extending patch-clamp recordings to awake animals free to explore their environments.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-1096-0_17}, author = {Lee, Albert K and Epsztein, J{\'e}r{\^o}me and Brecht, Michael} } @article {2694, title = {Intracellular determinants of hippocampal CA1 place and silent cell activity in a novel environment.}, journal = {Neuron}, volume = {70}, year = {2011}, month = {2011 Apr 14}, pages = {109-20}, abstract = {

For each environment a rodent has explored, its hippocampus contains a map consisting of a unique subset of neurons, called place cells, that have spatially tuned spiking there, with the remaining neurons being essentially silent. Using whole-cell recording in freely moving rats exploring a novel maze, we observed differences in intrinsic cellular properties and input-based subthreshold membrane potential levels underlying this division into place and silent cells. Compared to silent cells, place cells had lower spike thresholds and peaked versus flat subthreshold membrane potentials as a function of animal location. Both differences were evident from the beginning of exploration. Additionally, future place cells exhibited higher burst propensity before exploration. Thus, internal settings appear to predetermine which cells will represent the next novel environment encountered. Furthermore, place cells fired spatially tuned bursts with large, putatively calcium-mediated depolarizations that could trigger plasticity and stabilize the new map for long-term storage. Our results provide new insight into hippocampal memory formation.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2011.03.006}, author = {Epsztein, J{\'e}r{\^o}me and Brecht, Michael and Lee, Albert K} } @article {1344, title = {Impact of spikelets on hippocampal CA1 pyramidal cell activity during spatial exploration.}, journal = {Science}, volume = {327}, year = {2010}, month = {2010 Jan 22}, pages = {474-7}, abstract = {

In vivo intracellular recordings of hippocampal neurons reveal the occurrence of fast events of small amplitude called spikelets or fast prepotentials. Because intracellular recordings have been restricted to anesthetized or head-fixed animals, it is not known how spikelet activity contributes to hippocampal spatial representations. We addressed this question in CA1 pyramidal cells by using in vivo whole-cell recording in freely moving rats. We observed a high incidence of spikelets that occurred either in isolation or in bursts and could drive spiking as fast prepotentials of action potentials. Spikelets strongly contributed to spiking activity, driving approximately 30\% of all action potentials. CA1 pyramidal cell firing and spikelet activity were comodulated as a function of the animal{\textquoteright}s location in the environment. We conclude that spikelets have a major impact on hippocampal activity during spatial exploration.

}, keywords = {Action Potentials, Animals, CA1 Region, Exploratory Behavior, Hippocampal, Male, Maze Learning, Patch-Clamp Techniques, Pyramidal Cells, Rats, Space Perception, Wistar}, issn = {1095-9203}, doi = {10.1126/science.1182773}, author = {Epsztein, J{\'e}r{\^o}me and Lee, Albert K and Chorev, Edith and Brecht, Michael} } @article {1343, title = {Head-anchored whole-cell recordings in freely moving rats.}, journal = {Nature Protocols}, volume = {4}, year = {2009}, month = {2009}, pages = {385-92}, abstract = {

Intracellular recordings are routinely used to study the synaptic and intrinsic properties of neurons in vitro. A key requirement for these recordings is a mechanically very stable preparation; thus their use in vivo had been limited previously to head-restrained animals. We have recently demonstrated that anchoring the electrode rigidly in place with respect to the skull provides sufficient stabilization for long-lasting, high-quality whole-cell recordings in awake, freely moving rats. This protocol describes our procedure in detail, adds specific instructions for targeting hippocampal CA1 pyramidal neurons and updates it with changes that facilitate patching and improve the success rate. The changes involve combining a standard, nonhead-mounted micromanipulator with a gripper to firmly hold the recording pipette during the anchoring process then gently release it afterwards. The procedure from the beginning of surgery to the end of a recording takes approximately 5 h. This technique allows new studies of the mechanisms underlying neuronal integration and cellular/synaptic plasticity in identified cells during natural behaviors.

}, keywords = {Animals, Brain, Electrodes, Implanted, Neurology, Neurons, Patch-Clamp Techniques, Rats, Wakefulness}, issn = {1750-2799}, doi = {10.1038/nprot.2009.5}, author = {Lee, Albert K and Epsztein, J{\'e}r{\^o}me and Brecht, Michael} } @article {1342, title = {Whole-cell recordings in freely moving rats.}, journal = {Neuron}, volume = {51}, year = {2006}, month = {2006 Aug 17}, pages = {399-407}, abstract = {

Intracellular recording, which allows direct measurement of the membrane potential and currents of individual neurons, requires a very mechanically stable preparation and has thus been limited to in vitro and head-immobilized in vivo experiments. This restriction constitutes a major obstacle for linking cellular and synaptic physiology with animal behavior. To overcome this limitation we have developed a method for performing whole-cell recordings in freely moving rats. We constructed a miniature head-mountable recording device, with mechanical stabilization achieved by anchoring the recording pipette rigidly in place after the whole-cell configuration is established. We obtain long-duration recordings (mean of approximately 20 min, maximum 60 min) in freely moving animals that are remarkably insensitive to mechanical disturbances, then reconstruct the anatomy of the recorded cells. This head-anchored whole-cell recording technique will enable a wide range of new studies involving detailed measurement and manipulation of the physiological properties of identified cells during natural behaviors.

}, keywords = {Animal, Animals, Behavior, Brain, Electrodes, Implanted, Male, Membrane Potentials, Microelectrodes, Neurons, Newborn, Patch-Clamp Techniques, Rats, Sprague-Dawley, Wakefulness, Wistar}, issn = {0896-6273}, doi = {10.1016/j.neuron.2006.07.004}, author = {Lee, Albert K and Manns, Ian D and Sakmann, Bert and Brecht, Michael} }