A transcriptional rheostat couples past activity to future sensory responses
Tatsuya Tsukahara, David H Brann, Stan L Pashkovski, Grigori Guitchounts, Thomas Bozza, Sandeep Robert Datta
Cell. 2021. Download PDF
Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state
Stable 3D Head Direction Signals in the Primary Visual Cortex
Grigori Guitchounts, William Lotter, Joel Dapello, David Cox
bioRxiv. 2020. Download PDF
The mammalian brain’s navigation system is informed in large part by visual signals. While the primary visual cortex (V1) is extensively interconnected with brain areas involved in computing head direction (HD) information, it is unknown to what extent navigation information is available in the population activity of visual cortex. To test whether information about head direction information is available in visual cortex, we recorded neuronal activity in V1 of freely behaving rats. We show that significant information about yaw, roll, and pitch of the head can be linearly decoded from V1 either in the presence or absence of visual cues. Individual V1 neurons were tuned to head direction, with a quarter of the neurons tuned to conjunctions of angles in all three planes. These results demonstrate the presence of a critical navigational signal in a primary cortical sensory area and support predictive coding theories of brain function.
Encoding of 3D Head Orienting Movements in Primary Visual Cortex
Grigori Guitchounts, Javier Masis, Steffen B.E. Wolff, and David Cox
Neuron. 2020. Download PDF
Animals actively sample the sensory world by generating complex patterns of movement that evolve in three dimensions. Whether or how such movements affect neuronal activity in sensory cortical areas remains largely unknown, because most experiments exploring movement-related modulation have been performed in head- fixed animals. Here, we show that 3D head-orienting movements (HOMs) modulate primary visual cortex (V1) activity in a direction-specific manner that also depends on light. We identify two overlapping populations of movement-direction-tuned neurons that support this modulation, one of which is direction tuned in the dark and the other in the light. Although overall movement enhanced V1 responses to visual stimulation, HOMs suppressed responses. We demonstrate that V1 receives a motor efference copy related to orientation from secondary motor cortex, which is involved in controlling HOMs. These results support predictive coding theories of brain function and reveal a pervasive role of 3D movement in shaping sensory cortical dynamics.
64-Channel Carbon Fiber Electrode Arrays for Chronic Electrophysiology
Grigori Guitchounts and David Cox
Scientific Reports. 2020. Download PDF
A chief goal in neuroscience is to understand how neuronal activity relates to behavior, perception, and cognition. However, monitoring neuronal activity over long periods of time is technically challenging, and limited, in part, by the invasive nature of recording tools. While electrodes allow for recording in freely-behaving animals, they tend to be bulky and stiff, causing damage to the tissue they are implanted in. One solution to this invasiveness problem may be probes that are small enough to fly under the immune system's radar. Carbon fiber (CF) electrodes are thinner and more flexible than typical metal or silicon electrodes, but the arrays described in previous reports had low channel counts and required time-consuming manual assembly. Here we report the design of an expanded-channel-count carbon fiber electrode array (CFEA) as well as a method for fast preparation of the recording sites using acid etching and electroplating with PEDOT-TFB, and demonstrate the ability of the 64-channel CFEA to record from rat visual cortex. We include designs for interfacing the system with micro-drives or flex-PCB cables for recording from multiple brain regions, as well as a facilitated method for coating CFs with the insulator Parylene-C. High-channel-count CFEAs may thus be an alternative to traditional microwire-based electrodes and a practical tool for exploring the neural code.
A Micro-CT-based method for quantitative brain lesion characterization and electrode localization
Javier Masís, David Mankus, Steffen BE Wolff, Grigori Guitchounts, Maximilian Joesch, David D Cox
Scientific Reports. 2018. Download PDF
Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro- electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods.
Unstable neurons underlie a stable learned behavior
William A Liberti III*, Jeffrey E Markowitz*, L Nathan Perkins, Derek C Liberti, Daniel P Leman, Grigori Guitchounts, Tarciso Velho, Darrell N Kotton, Carlos Lois, Timothy J Gardner
Nature Neuroscience. 2016. Download PDF
Motor skills can be maintained for decades, but the biological basis of this memory persistence remains largely unknown. The zebra finch, for example, sings a highly stereotyped song that is stable for years, but it is not known whether the precise neural patterns underlying song are stable or shift from day to day. Here we demonstrate that the population of projection neurons coding for song in the premotor nucleus, HVC, change from day to day.
Mesoscopic patterns of neural activity support songbird cortical sequences
Jeffrey E Markowitz*, William A Liberti III*, Grigori Guitchounts, Tarciso Velho, Carlos Lois, Timothy J Gardner
PLoS Biology. 2015. Download PDF.
Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From “time cells” in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity.
A carbon-fiber electrode array for long-term neural recording
Grigori Guitchounts*, Jeffrey E Markowitz*, William A Liberti*, Timothy J Gardner
Journal of Neural Engineering. 2013. Download PDF.
Chronic neural recording in behaving animals is an essential method for studies of neural circuit function. However, stable recordings from small, densely packed neurons remains challenging, particularly over time-scales relevant for learning. We describe an assembly method for a 16 channel electrode array consisting of carbon fibers (<5 μm diameter) individually insulated with Parylene-C and fire-sharpened. The diameter of the array is approximately 26 microns, along the full extent of the implant. Carbon fiber arrays were tested in HVC (used as a proper name), a song motor nucleus, of singing zebra finches where individual neurons discharge with temporally precise patterns. Previous reports of activity in this population of neurons has required the use of high impedance electrodes on movable microdrives. Here, the carbon fiber electrodes provided stable multi-unit recordings over time-scales of months.
THE TWO ETOMIDATE SITES IN Α1Β2Γ2 GABAA RECEPTORS CONTRIBUTE EQUALLY AND NON-COOPERATIVELY TO MODULATION OF CHANNEL GATING
Grigori Guitchounts, Deirdre S Stewart, Stuart A Forman
Anesthesiology. 2012. Download PDF.
Etomidate is a potent hypnotic agent that acts via γ-aminobutyric acid type A (GABAA) receptors. Evidence supports the presence of two etomidate sites per GABAA receptor, and current models assume that each site contributes equally and non-cooperatively to drug effects. These assumptions remain untested. We used concatenated dimer (β2-α1) and trimer (γ2-β2-α1) GABAA subunit assemblies that form functional α1β2γ2 channels, and inserted α1M236W etomidate site mutations into both dimers (β2-α1M236W) and trimers (γ2-β2-α1M236W)...