scholarly journals Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Justin K O'Hare ◽  
Haofang Li ◽  
Namsoo Kim ◽  
Erin Gaidis ◽  
Kristen Ade ◽  
...  
Keyword(s):  
Behavioral Adaptation ◽  
Single Class ◽  
Gamma Frequency ◽  
Dependent Behavior ◽  
Selective Modulation ◽  
Lever Pressing ◽  
Fast Spiking ◽  
Habitual Behavior ◽  
Circuit Output

Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

scholarly journals Striatal fast-spiking interneurons drive habitual behavior

2017 ◽  
Author(s):  
Justin K. O’Hare ◽  
Haofang Li ◽  
Namsoo Kim ◽  
Erin Gaidis ◽  
Kristen K. Ade ◽  
...  
Keyword(s):  
Habit Formation ◽  
Behavioral Adaptation ◽  
Single Class ◽  
Gamma Frequency ◽  
Dependent Behavior ◽  
Selective Modulation ◽  
Lever Pressing ◽  
Fast Spiking ◽  
Habitual Behavior

AbstractHabit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

scholarly journals The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons

2011 ◽  
Vol 106 (6) ◽  
pp. 2936-2949 ◽  
Author(s):  
Giuseppe Sciamanna ◽  
Charles J. Wilson
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Repetitive Firing ◽  
Spike Threshold ◽  
Gamma Frequency ◽  
Subthreshold Oscillations ◽  
Fast Spiking

Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16–23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1–1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo.

scholarly journals Author response: Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior

2017 ◽  
Author(s):  
Justin K O'Hare ◽  
Haofang Li ◽  
Namsoo Kim ◽  
Erin Gaidis ◽  
Kristen Ade ◽  
...  
Keyword(s):  
Author Response ◽  
Fast Spiking ◽  
Habitual Behavior ◽  
Circuit Output

scholarly journals A novel weight lifting task for investigating effort and persistence in rats

2019 ◽  
Author(s):  
Blake Porter ◽  
Kristin L. Hillman
Keyword(s):  
Food Delivery ◽  
Video Tracking ◽  
Weight Lifting ◽  
Recording Equipment ◽  
Single Plane ◽  
Action Sequence ◽  
Total N ◽  
Lever Pressing ◽  
Lifting Task

AbstractHere we present a novel effort-based task for laboratory rats: the weight lifting task (WLT). Studies of effort expenditure in rodents have typically involved climbing barriers within T-mazes or operant lever pressing paradigms. These task designs have been successful for neuropharmacological and neurophysiological investigations, but both tasks involve simple action patterns prone to automatization. Furthermore, high climbing barriers present risk of injury to animals and/or tethered recording equipment. In the WLT, a rat is placed in a large rectangular arena and tasked with pulling a rope 30 cm to trigger food delivery at a nearby spout; weights can be added to the rope in 45 g increments to increase the intensity of effort. As compared to lever pressing and barrier jumping, 30 cm of rope pulling is a multi-step action sequence requiring sustained effort. The actions are carried out on the single plane of the arena floor, making it safer for the animal and more suitable for tethered equipment and video tracking. A microcontroller and associated sensors enable precise timestamping of specific behaviors to synchronize with electrophysiological recordings. The rope and reward spout are spatially segregated to allow for spatial discrimination of the effort zone and the reward zone. We validated the task across five cohorts of rats (total n=35) and report consistent behavioral metrics. The WLT is well-suited for neuropharmacological and/or in vivo neurophysiological investigations surrounding effortful behaviors, particularly when wanting to probe different aspects of effort expenditure (intensity vs. duration).

Cytoplasmic and nuclear progesterone receptors in mouse mammary tumours during pregnancy determined by an improved hydroxylapatite assay

1982 ◽  
Vol 94 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Y. Koseki ◽  
M. E. Costlow ◽  
D. Cole ◽  
A. Matsuzawa
Keyword(s):  
Progesterone Receptors ◽  
Nuclear Extract ◽  
Scatchard Analysis ◽  
Normal Mammary Gland ◽  
Single Class ◽  
Heat Stable ◽  
Nuclear Extracts ◽  
Complete Exchange

The binding of [3H] 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (R5020) to progesterone receptors in cytosol and nuclear extracts (0·6 m-KCl) of the pregnancy-dependent, TPDMT-4 mouse mammary tumour was measured at various stages of pregnancy. Compared with conventional dextran-coated charcoal (DCC) assays, a hydroxylapatite assay with DCC pretreatment and precharging of the cytosol with unlabelled R5020 (4 × 10−8 mol/l, for 3–4 h at 4 °C) showed the highest level of binding. The DCC treatment markedly increased the level of R5020 binding in both cytosol and nuclear extracts by allowing the receptor to bind to hydroxylapatite. The DCC pretreatment apparently removed a heat-stable and non-dialysable factor which prevented the receptor from binding to the hydroxylapatite. Using this assay R5020 binding reached a steady state in 24 h at 4 °C, with complete exchange of radioactive for non-radioactive ligand by 20 h. Nuclear extracts did not require precharging and complete exchange was more rapid. Scatchard analysis (without precharging) disclosed a single class of binding sites with a dissociation constant for cytosol of 3·2 ± 0·8 (s.e.m.) × 10−9 mol/l (n = 3) and 4·7 ± 0·6 × 10−9 mol/l (n = 5) for the nuclear extract. Binding was hormone-specific and progesterone translocated binding from the cytoplasm to the nucleus both in vivo and in vitro. Translocation, however, led to a substantial loss of total (nuclear + cytoplasmic receptors. During pregnancy, cytoplasmic progesterone receptor levels were unchanged and low compared to nuclear progesterone receptors which increased by sevenfold from days 1 to 11 and then decreased at day 16. Compared with recent data on cytoplasmic progesterone receptors in normal mammary gland, our results suggested that this tumour may have a reduced sensitivity to the down-regulatory activity of progesterone. This lesion may, in part, account for the failure of the tumour to differentiate during pregnancy.

Characterization of glomerular thromboxane receptor sites in the rat

1989 ◽  
Vol 256 (6) ◽  
pp. F1111-F1116 ◽  
Author(s):  
B. M. Wilkes ◽  
J. Solomon ◽  
M. Maita ◽  
P. F. Mento
Keyword(s):  
Specific Binding ◽  
Binding Studies ◽  
Single Class ◽  
Thromboxane Receptor ◽  
Renal Glomeruli ◽  
Receptor Sites ◽  
High Affinity Receptor ◽  
Pg E2 ◽  
Txa2 Receptor Antagonist

The aim of this study was to identify and characterize thromboxane (Tx) receptor sites in renal glomeruli. Binding studies were performed on freshly isolated glomeruli using the stable TxA2 receptor antagonist, [3H]SQ 29548. Specific binding was saturable, reversible, and varied with glomerular protein. Scatchard plots revealed a single class of high-affinity receptor sites (Kd = 14.3 +/- 2.4 nM, Bmax = 361 +/- 22 fmol/mg; n = 5). Specific binding was inhibited by Tx agonists (U-46619 and U-44069) and antagonist (SQ 29548) and was highly specific for Tx, since prostaglandin (PG)E2 and PGF2 alpha were 1,000-fold less potent in inhibiting binding. In vivo, U-46619 (1.75 micrograms.kg-1.min-1) was without effect on mean arterial pressure, but reduced renal blood flow by 71% (P less than 0.01) and glomerular filtration rate by 67% (P less than 0.01) and increased filtration fraction by 24% (P less than 0.05). SQ 29548 (10 micrograms.kg-1.min-1) completely blocked the renal effects of U-46619. These studies demonstrate the presence of specific receptor sites for Tx on renal glomeruli that are linked to modulation of renal hemodynamics.

Auditory Thalamocortical Transmission Is Reliable and Temporally Precise

2005 ◽  
Vol 94 (3) ◽  
pp. 2019-2030 ◽  
Author(s):  
Heather J. Rose ◽  
Raju Metherate
Keyword(s):  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Latency Variability ◽  
Medial Geniculate ◽  
Low Jitter ◽  
Fast Spiking ◽  
Whole Cell Recordings ◽  
Minimal Stimulation ◽  
Juvenile Mouse

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. “Minimal” stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was ∼1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2–300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates ≥40 Hz, EPSPs also summed to activate N-methyl-d-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.

scholarly journals Beyond spikes: Multiscale computational analysis of in vivo long-term recordings in the cockroach circadian clock

2019 ◽  
Vol 3 (4) ◽  
pp. 944-968 ◽  
Author(s):  
Pablo Rojas ◽  
Jenny A. Plath ◽  
Julia Gestrich ◽  
Bharath Ananthasubramaniam ◽  
Martin E. Garcia ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Field Potential ◽  
Dynamic Features ◽  
Pigment Dispersing Factor ◽  
Gamma Frequency ◽  
Accessory Medulla ◽  
Electrophysiological Recordings ◽  
Wide Range

The circadian clock of the nocturnal Madeira cockroach is located in the accessory medulla, a small nonretinotopic neuropil in the brain’s visual system. The clock comprises about 240 neurons that control rhythms in physiology and behavior such as sleep-wake cycles. The clock neurons contain an abundant number of partly colocalized neuropeptides, among them pigment-dispersing factor (PDF), the insects’ most important circadian coupling signal that controls sleep-wake rhythms. We performed long-term loose-patch clamp recordings under 12:12-hr light-dark cycles in the cockroach clock in vivo. A wide range of timescales, from milliseconds to seconds, were found in spike and field potential patterns. We developed a framework of wavelet transform–based methods to detect these multiscale electrical events. We analyzed frequencies and patterns of events with interesting dynamic features, such as mixed-mode oscillations reminiscent of sharp-wave ripples. Oscillations in the beta/gamma frequency range (20–40 Hz) were observed to rise at dawn, when PDF is released, peaking just before the onset of locomotor activity of the nocturnal cockroach. We expect that in vivo electrophysiological recordings combined with neuropeptide/antagonist applications and behavioral analysis will determine whether specific patterns of electrical activity recorded in the network of the cockroach circadian clock are causally related to neuropeptide-dependent control of behavior.

scholarly journals Inhibitory Effects of Calcitriol on the Growth of MCF-7 Breast Cancer Xenografts in Nude Mice: Selective Modulation of Aromatase Expression in vivo

2011 ◽  
Vol 2 (3) ◽  
pp. 190-202 ◽  
Author(s):  
Srilatha Swami ◽  
Aruna V. Krishnan ◽  
Jennifer Y. Wang ◽  
Kristin Jensen ◽  
Lihong Peng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Inhibitory Effects ◽  
Aromatase Expression ◽  
Selective Modulation ◽  
Breast Cancer Xenografts ◽  
Mcf 7
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