Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating ...cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.
Rationale
The infralimbic cortex (IL) and its downstream projection target the nucleus accumbens shell (NAshell) mediate the active suppression of cocaine-seeking behavior. Although an optogenetic ...approach would be beneficial for stimulating the IL and its efferents to study their role during reinstatement of cocaine seeking, the use of channelrhodopsin introduces significant difficulties, as optimal stimulation parameters are not known.
Objectives
The present experiments utilized a stable step-function opsin (SSFO) to potentiate endogenous activity in the IL and in IL terminals in the NAshell during cocaine-seeking tests to determine how these manipulations affect cocaine-seeking behaviors.
Methods
Rats first underwent 6-h access cocaine self-administration followed by 21–27 days in the homecage. Rats then underwent cue-induced and cocaine-primed drug-seeking tests during which the optogenetic manipulation was given. The same rats then underwent extinction training, followed by cue-induced and cocaine-primed reinstatements.
Results
Potentiation of endogenous IL activity did not significantly alter cue-induced or cocaine-primed drug seeking following the homecage period. However, following extinction training, enhancement of endogenous IL activity attenuated cue-induced reinstatement by 35% and cocaine-primed reinstatement by 53%. Stimulation of IL terminals in the NAshell did not consistently alter cocaine-seeking behavior.
Conclusion
These results suggest the utility of an SSFO-based approach for enhancing activity in a structure without driving specific patterns of neuronal firing. However, the utility of an SSFO-based approach for axon terminal stimulation remains unclear. Moreover, these results suggest that the ability of the IL to reduce cocaine seeking depends, at least in part, on rats first having undergone extinction training.
Abstract
A measurement of the double-polarization observable
E
for the reaction
$$\gamma p\rightarrow \pi ^0 p$$
γ
p
→
π
0
p
is reported. The data were taken with the CBELSA/TAPS experiment at the ...ELSA facility in Bonn using the Bonn frozen-spin butanol (C
$$_4$$
4
H
$$_9$$
9
OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from
$$E_\gamma =600$$
E
γ
=
600
to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.
A measurement of the double-polarization observable E for the reaction γp→π0p is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin ...butanol (C4H9OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from Eγ=600 to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.
A measurement of the double-polarization observable
E
for the reaction
γ
p
→
π
0
p
is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn ...frozen-spin butanol (C
4
H
9
OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from
E
γ
=
600
to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.
A measurement of the double-polarization observable
E
for the reaction
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\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
...\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$\gamma p\rightarrow \pi ^0 p$$\end{document}
γ
p
→
π
0
p
is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C
\documentclass12pt{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$_4$$\end{document}
4
H
\documentclass12pt{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$_9$$\end{document}
9
OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from
\documentclass12pt{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$E_\gamma =600$$\end{document}
E
γ
=
600
to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.
The first measurements of the beam-target-helicity-asymmetries E and G in the photoproduction of ω-mesons off protons at the CBELSA/TAPS experiment are reported. E (G) was measured using circularly ...(linearly) polarised photons and a longitudinally polarised target. E was measured over the photon energy range from close to threshold (Eγ=1108 MeV) to Eγ=2300 MeV and G at a single energy interval of 1108<Eγ<1300 MeV. Both measurements cover the full solid angle. The observables E and G are highly sensitive to the contribution of baryon resonances, with E acting as a helicity filter in the s-channel. The new results indicate significant s-channel resonance contributions together with contributions from t-channel exchange processes. A partial wave analysis reveals strong contributions from the partial waves with spin-parity JP=3/2+,5/2+, and 3/2−.
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