| 1. |
- Moulin, Thiago C., et al.
(författare)
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Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus
- 2019
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 29:8, s. 755-761
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Tidskriftsartikel (refereegranskat)abstract
- Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.
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| 2. |
- Siwani, Samer, et al.
(författare)
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Hippocampal OLMα2 cells gate basolateral amygdala inputs for threat processing
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- It is becoming increasingly clear that the hippocampus is functionally diverse across its longitudinal axis. The ventral hippocampus is known to participate anxiety-related behaviors and may, together with the basolateral amygdala (BLA), facilitate threat aversion. Nevertheless, studies of mechanisms and circuit organization for processing value related cues are scarce. Here we investigate a microcircuit involving a subgroup of interneurons, referred to as Oriens lacunosum-moleculare cells, defined by their expression of the nicotinic receptor alpha2 subunit (OLMα2). Such cells can bidirectionally affect the response to predator odor as well as the encoding of object memories. In tracing experiments, we found that the basolateral amygdala mainly projects to the ventral hippocampus, whereas the medial amygdala and claustrum projects to the intermediate hippocampus. Moreover, we found that BLA inputs inhibit intrinsic hippocampal slow oscillation. Optogenetic stimulation of OLMα2 cells in the intermediate hippocampus caused an increase in approach of objects. Inhibition of ventrally located OLMα2 cells cause an increased avoidance to natural aversive stimuli and could entrain aversion to value neutral odors. In contrast, theta II oscillations, which predominantly appear in the ventral hippocampus during anxiety related behaviors, were absent during object recognition. Theta II oscillations only appeared when the animal was naïve to the arena setting. We conclude that there are functional differences between the intermediate and ventral hippocampus and that OLMα2 cells, in addition to sensory inputs, process emotional value signals from the amygdala.
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| 3. |
- Winne, Jessica, et al.
(författare)
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Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT
- 2020
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Ingår i: Experimental Neurology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0014-4886 .- 1090-2430. ; 326
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Tidskriftsartikel (refereegranskat)abstract
- Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5-month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1 h after salicylate (300 mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.
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| 4. |
- Winne, Jessica, et al.
(författare)
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Salicylate induces anxiety-like behavior and slow theta oscillation and abolishes the relationship between running speed and fast theta oscillation frequency
- 2019
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Ingår i: Hippocampus. - : WILEY. - 1050-9631 .- 1098-1063. ; 29:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- Salicylate intoxication is a cause of tinnitus in humans and it is often used to produce tinnitus-like perception in animal models. Here, we assess whether salicylate induces anxiety-like electrophysiological and behavioral signs. Using microwire electrode arrays, we recorded local field potential in the ventral and, in some experiments dorsal hippocampus, in an open field arena 1 hr after salicylate (300 mg/kg) injection. We found that animals treated with salicylate moved dramatically less than saline treated animals. Salicylate-treated animals showed a strong 4-6 Hz (type 2) oscillation in the ventral hippocampus (with smaller peaks in dorsal hippocampus electrodes). Coherence in the 4-6 Hz-theta band was low in the ventral and dorsal hippocampus when compared to movement-related theta coherence (7-10 Hz). Moreover, movement related theta oscillation frequency decreased and its dependency on running speed was abolished. Our results suggest that salicylate-induced theta is mostly restricted to the ventral hippocampus. Slow theta has been classically associated to anxiety-like behaviors. Here, we show that salicylate application can consistently generate low frequency theta in the ventral hippocampus. Tinnitus and anxiety show strong comorbidity and the increase in ventral hippocampus low frequency theta could be part of this association.
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