Dopaminergic modulation of basal ganglia output through coupled excitation–inhibition

Learning and maintenance of skilled movements require exploration of motor space and selection of appropriate actions. Vocal learning and social context-dependent plasticity in songbirds depend on a basal ganglia circuit, which actively generates vocal variability. Dopamine in the basal ganglia reduces trial-to-trial neural variability when the bird engages in courtship song. Here, we present evidence for a unique, tonically active, excitatory interneuron in the songbird basal ganglia that makes strong synaptic connections onto output pallidal neurons, often linked in time with inhibitory events. Dopamine receptor activity modulates the coupling of these excitatory and inhibitory events in vitro, which results in a dynamic change in the synchrony of a modeled population of basal ganglia output neurons receiving excitatory and inhibitory inputs. The excitatory interneuron thus serves as one biophysical mechanism for the introduction or modulation of neural variability in this circuit.

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Microcircuits of the Striatum

Handbook of Brain Microcircuits ◽

10.1093/med/9780190636111.003.0011 ◽

2017 ◽

pp. 121-132

Author(s):

Natalie M. Doig ◽

J. Paul Bolam

Keyword(s):

Basal Ganglia ◽

Caudate Nucleus ◽

Internal Capsule ◽

Projection Neurons ◽

Gabaergic Interneurons ◽

Cholinergic Interneurons ◽

Spiny Neurons ◽

Output Neurons ◽

Major Division ◽

Selection Of

The striatum (or caudate-putamen, or caudate nucleus and putamen in those species in which they are divided by the internal capsule) is the major division of the basal ganglia, a group of structures involved in a variety of processes, including movement and cognitive and mnemonic functions. The striatum consists of a population of principal neurons, the medium-sized, densely spiny neurons (MSNs)—accounting for up to 97% of all neurons depending on species—which are the projection neurons of the striatum, several populations of GABAergic interneurons, and a population of cholinergic interneurons. The principal afferents of the striatum are glutamatergic, are derived from the cortex and thalamus, and mainly innervate the spines of MSNs. The essential computation performed by the striatum is the decision about which MSNs will fire, the consequence of which is altered firing of basal ganglia output neurons, and hence the selection of the basal ganglia–associated behavior.

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Optogenetic activation of the inhibitory nigro-collicular circuit evokes orienting movements in mice

10.1101/2020.05.21.107680 ◽

2020 ◽

Author(s):

C.A. Villalobos ◽

M.A. Basso

Keyword(s):

Basal Ganglia ◽

Substantia Nigra ◽

High Frequency ◽

Current Model ◽

Optogenetic Stimulation ◽

Output Neurons ◽

Rebound Spiking ◽

Stimulation Of

ABSTRACTIn contrast to predictions from the current model of basal ganglia (BG) function, we report here that increasing inhibition from the BG to the superior colliculus (SC) through the substantia nigra (nigra) using in vivo optogenetic activation of GABAergic terminals in mice, produces contralateral orienting movements. Orienting movements resulting from activation of inhibitory nigral terminals are unexpected because decreases and not increases, in nigral activity are generally associated with orienting movements. To determine how orienting movements may result from activation of inhibitory terminals, we performed a series of slice experiments and found that the same optogenetic stimulation of nigral terminals used in vivo, evoked post-inhibitory rebound depolarization and spiking in SC output neurons in vitro. Only high frequency (100Hz) stimulation evoked contralateral movements in vivo and triggered rebound spiking in vitro. The latency of orienting movements relative to the stimulation in vivo was similar to the latency of rebound spiking in vitro. Taken together, our results point toward a novel hypothesis that inhibition from the BG may play an active rather than passive role in the generation of orienting movements in mice.

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In vitro negative selection of viral superantigen-reactive TCR transgenic thymocytes by thymic dendritic cells

Immunology Letters ◽

10.1016/s0165-2478(97)87831-5 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 249

Author(s):

I Ferrero

Keyword(s):

Dendritic Cells ◽

Negative Selection ◽

Selection Of

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Clone selection of in vitro horseradish hairy root cultures

Planta Medica ◽

10.1055/s-0035-1565606 ◽

2015 ◽

Vol 81 (16) ◽

Author(s):

R Bertóti ◽

Á Alberti ◽

A Böszörményi ◽

R Könye ◽

T Horváth ◽

...

Keyword(s):

Hairy Root ◽

Hairy Root Cultures ◽

Root Cultures ◽

Clone Selection ◽

Selection Of

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Faculty Opinions recommendation of In vitro selection of a deoxyribozyme that can utilize multiple substrates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004319.49956 ◽

2002 ◽

Author(s):

Niles Lehman

Keyword(s):

In Vitro Selection ◽

Multiple Substrates ◽

Selection Of

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Faculty Opinions recommendation of CIS display: In vitro selection of peptides from libraries of protein-DNA complexes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017658.206556 ◽

2004 ◽

Author(s):

Sachdev Sidhu

Keyword(s):

In Vitro Selection ◽

Dna Complexes ◽

Selection Of

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Faculty Opinions recommendation of Molecular microcircuitry underlies functional specification in a basal ganglia circuit dedicated to vocal learning.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13941958.15387102 ◽

2012 ◽

Author(s):

Genevieve Konopka

Keyword(s):

Basal Ganglia ◽

Vocal Learning ◽

Functional Specification

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The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-9-10-3-7 ◽

2020 ◽

Vol 65 (9-10) ◽

pp. 3-7

Author(s):

V. V. Gostev ◽

Yu. V. Sopova ◽

O. S. Kalinogorskaya ◽

M. E. Velizhanina ◽

I. V. Lazareva ◽

...

Keyword(s):

Staphylococcus Aureus ◽

In Vitro Selection ◽

Methicillin Resistant Staphylococcus Aureus ◽

High Concentration ◽

Short Term ◽

High Concentrations ◽

Selection Of ◽

Selection Of Resistance ◽

Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

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