Efficient sorting of single-unit activity from midbrain cells using KiloSort is as accurate as manual sorting

Allen, Madeleine C; Chowdhury, Tara G.; Wegener, Meredyth A; Moghaddam, Bita

doi:10.1101/303479

Cited by 5 publications

(5 citation statements)

References 7 publications

(5 reference statements)

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“…Spikes were amplified at 1000Â gain, digitized at 40 kHz, and single-unit data were bandpass filtered at 300 Hz. Single units were isolated in Kilosort (Allen et al, 2018) or Offline Sorter (Plexon) using a combination of manual and semiautomatic sorting techniques until each unit is well isolated in state space (minimum acceptable signal-to-noise ratio ;2.5:1). Neurons were not screened for specific physiological characteristics or response properties before recording.…”

Section: Electrophysiologymentioning

confidence: 99%

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

et al. 2021

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Neuronal underpinning of learning cause-and-effect associations in the adolescent brain remains poorly understood. Two fundamental forms of associative learning are Pavlovian (classical) conditioning, where a stimulus is followed by an outcome, and operant (instrumental) conditioning, where outcome is contingent on action execution. Both forms of learning, when associated with a rewarding outcome, rely on midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SN). We find that, in adolescent male rats, reward-guided associative learning is encoded differently by midbrain dopamine neurons in each conditioning paradigm. Whereas simultaneously recorded VTA and SN adult neurons have a similar phasic response to reward delivery during both forms of conditioning, adolescent neurons display a muted reward response during operant but a profoundly larger reward response during Pavlovian conditioning. These results suggest that adolescent neurons assign a different value to reward when it is not gated by action. The learning rate of adolescents and adults during both forms of conditioning was similar, supporting the notion that differences in reward response in each paradigm may be because of differences in motivation and independent of state versus action value learning. Static characteristics of dopamine neurons, such as dopamine cell number and size, were similar in the VTA and SN of both ages, but there were age-related differences in stimulated dopamine release and correlated spike activity, suggesting that differences in reward responsiveness by adolescent dopamine neurons are not because of differences in intrinsic properties of these neurons but engagement of different dopaminergic networks.SIGNIFICANCE STATEMENTReckless behavior and impulsive decision-making by adolescents suggest that motivated behavioral states are encoded differently by the adolescent brain. Motivated behavior, which is dependent on the function of the dopamine system, follows learning of cause-and-effect associations in the environment. We find that dopamine neurons in adolescents encode reward differently depending on the cause-and-effect relationship of the means to receive that reward. Compared with adults, reward contingent on action led to a muted response, whereas reward that followed a cue but was not gated by action produced an augmented phasic response. These data demonstrate an age-related difference in dopamine neuron response to reward that is not uniform and is guided by processes that differentiate between state and action values.

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Section: Electrophysiologymentioning

confidence: 99%

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

et al. 2021

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“…Spikes were amplified at 1000x gain, digitized at 40 kHz, and single-unit data was band-pass filtered at 300 Hz by the recording software (Plexon, Dallas, TX). Single units were isolated in Kilosort as described previously [19].…”

Section: Electrophysiology and Behaviormentioning

confidence: 99%

Sex and strain differences in dynamic and static properties of the mesolimbic dopamine system

Rivera-Garcia

McCane

Chowdhury

et al. 2020

Neuropsychopharmacol.

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Sex is a biological variable that contributes to the incidence, clinical course, and treatment outcome of brain disorders. Chief among these are disorders associated with the dopamine system. These include Parkinson's disease, ADHD, schizophrenia, and mood disorders, which show stark differences in prevalence and outcome between men and women. In order to reveal the influence of biological sex as a risk factor in these disorders, there is a critical need to collect fundamental information about basic properties of the dopamine system in males and females. In Long Evans rats, we measured dynamic and static properties related to the mesolimbic dopamine system. Static measures included assessing ventral tegmental area (VTA) dopamine cell number and volume and expression of tyrosine hydroxylase and dopamine transporter. Dynamic measures in behaving animals included assessing (1) VTA neuronal encoding during learning of a cue-action-reward instrumental task and (2) dopamine release in the nucleus accumbens in response to electrical stimulation of the VTA, vesicular depletion of dopamine, and amphetamine. We found little or no sex difference in these measures, suggesting sexual congruency in fundamental static and dynamic properties of dopamine neurons. Thus, dopamine related sex-differences are likely mediated by secondary mechanisms that flexibly influence the function of the dopamine cells and circuits. Finally, we noted that most behavioral sex differences had been reported in Sprague-Dawley rats and repeated some of the above measures in that strain. We found some sex differences in those animals highlighting the importance of considering strain differences in experimental design and result interpretation.

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“…Although spikes are easier to interpret, there is a general concern of sufficient spike sorting with high-density probes, a problem that is more apparent with commercially available probes exceeding hundreds of recording sites ( 41 , 73 , 84 , 86 ). With extremely high-density probes (such as Neuropixels), sorting occurs automatically, using data from all channels simultaneously ( 48 , 108 ). Even with a simple multi-channel electrode design like ours, not only does one electrode detect multiple neurons, but the same neuron may be detected on multiple electrodes.…”

Section: Discussionmentioning

confidence: 99%

Chronic, Multi-Site Recordings Supported by Two Low-Cost, Stationary Probe Designs Optimized to Capture Either Single Unit or Local Field Potential Activity in Behaving Rats

et al. 2021

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Rodent models of cognitive behavior have greatly contributed to our understanding of human neuropsychiatric disorders. However, to elucidate the neurobiological underpinnings of such disorders or impairments, animal models are more useful when paired with methods for measuring brain function in awake, behaving animals. Standard tools used for systems-neuroscience level investigations are not optimized for large-scale and high-throughput behavioral battery testing due to various factors including cost, time, poor longevity, and selective targeting limited to measuring only a few brain regions at a time. Here we describe two different “user-friendly” methods for building extracellular electrophysiological probes that can be used to measure either single units or local field potentials in rats performing cognitive tasks. Both probe designs leverage several readily available, yet affordable, commercial products to facilitate ease of production and offer maximum flexibility in terms of brain-target locations that can be scalable (32–64 channels) based on experimental needs. Our approach allows neural activity to be recorded simultaneously with behavior and compared between micro (single unit) and more macro (local field potentials) levels of brain activity in order to gain a better understanding of how local brain regions and their connected networks support cognitive functions in rats. We believe our novel probe designs make collecting electrophysiology data easier and will begin to fill the gap in knowledge between basic and clinical research.

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Efficient sorting of single-unit activity from midbrain cells using KiloSort is as accurate as manual sorting

Cited by 5 publications

References 7 publications

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

Sex and strain differences in dynamic and static properties of the mesolimbic dopamine system

Chronic, Multi-Site Recordings Supported by Two Low-Cost, Stationary Probe Designs Optimized to Capture Either Single Unit or Local Field Potential Activity in Behaving Rats

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