Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats

Abstract The locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 msec or 10 sec accelerated acquisition of a similar odor discrimination. Similar odor discrimination learning was impaired by noradrenergic blockade in the piriform cortex (PC). However, 10-Hz phasic light-mediated learning facilitation was prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting a LC-VTA-PC dopamine circuitry involvement. Ten hertz tonic stimulation did not alter odor discrimination acquisition, and was ineffective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced conditioned odor aversion, while 10-Hz phasic stimulations produced an odor preference. Both conditionings were prevented by noradrenergic blockade in the basolateral amygdala (BLA). Cholera Toxin B retro-labeling showed larger engagement of nucleus accumbens-projecting neurons in the BLA with 10-Hz phasic activation, and larger engagement of central amygdala projecting cells with 25-Hz tonic light. These outcomes argue that the LC activation patterns differentially influence both target networks and behavior.

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Locus coeruleus patterns differentially modulate learning and valence in rat via the ventral tegmental area and basolateral amygdala respectively

10.1101/2020.04.17.047126 ◽

2020 ◽

Author(s):

Abhinaba Ghosh ◽

Faghihe Massaeli ◽

Kyron D. Power ◽

Tamunotonye Omoluabi ◽

Sarah E. Torraville ◽

...

Keyword(s):

Locus Coeruleus ◽

Ventral Tegmental Area ◽

Basolateral Amygdala ◽

Odor Discrimination ◽

Odor Aversion ◽

Odor Preference ◽

Learning Facilitation ◽

Ventral Tegmental ◽

Positive Valence ◽

Tonic Stimulation

ABSTRACTThe locus coeruleus (LC), the main source of forebrain norepinephrine, produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence coding of sensory information are unknown. Here bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 msec or 10 sec accelerates acquisition of a food-rewarded similar odor discrimination, but not a dissimilar odor discrimination, consistent with LC-supported enhanced pattern separation and plasticity. Similar odor discrimination learning is impaired by noradrenergic blockade in the piriform cortex (PC). However, here 10-Hz LC phasic light-mediated learning facilitation is prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting an LC-VTA-PC dopamine circuitry mediates 10-Hz phasic learning facilitation. Tonic stimulation at 10 Hz did not alter odor discrimination acquisition, and was less effective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced freezing, anxiety and conditioned odor aversion, while 10-Hz phasic stimulation produced an odor preference consistent with positive valence. Noradrenergic blockade in the basolateral amygdala (BLA) prevented conditioned odor preference and aversion induced by 10-Hz phasic and 25-Hz tonic light respectively. CTB retro-labeling showed relatively larger engagement of nucleus accumbens projecting neurons over central amygdala projecting neurons in the BLA with 10-Hz LC phasic activation, compared to 25-Hz tonic. These outcomes argue that LC pauses, as well as LC firing frequencies, differentially influence both target networks and behaviour.

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Odor discrimination learning is correlated with reduced after-hyperpolarization in piriform cortex pyramidal cells

Neuroscience Letters ◽

10.1016/s0304-3940(97)90175-0 ◽

1997 ◽

Vol 237 ◽

pp. S43

Author(s):

D. Saar ◽

Y. Grossman ◽

E. Barkai

Keyword(s):

Discrimination Learning ◽

Piriform Cortex ◽

Pyramidal Cells ◽

Odor Discrimination

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Brain fMRI during orientation selective epidural spinal cord stimulation

Scientific Reports ◽

10.1038/s41598-021-84873-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Antonietta Canna ◽

Lauri J. Lehto ◽

Lin Wu ◽

Sheng Sang ◽

Hanne Laakso ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Stimulation ◽

Pain Treatment ◽

Positive Impact ◽

Sensory Information ◽

Activation Patterns ◽

Promising Tool ◽

Cord Injury ◽

Epidural Spinal Cord Stimulation ◽

Brain Fmri

AbstractEpidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

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Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22094667 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4667

Author(s):

Michaela Shishmanova-Doseva ◽

Dimitrinka Atanasova ◽

Yordanka Uzunova ◽

Lyubka Yoanidu ◽

Lyudmil Peychev ◽

...

Keyword(s):

Oxidative Stress ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Basolateral Amygdala ◽

Neuronal Damage ◽

Piriform Cortex ◽

Preference Test ◽

Neuroprotective Activity ◽

Object Recognition Test ◽

Beneficial Effects

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

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The distributed circuit within the piriform cortex makes odor discrimination robust

The Journal of Comparative Neurology ◽

10.1002/cne.24492 ◽

2018 ◽

Vol 526 (17) ◽

pp. 2725-2743 ◽

Cited By ~ 10

Author(s):

Shyam Srinivasan ◽

Charles F. Stevens

Keyword(s):

Piriform Cortex ◽

Odor Discrimination

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SAT-606 Distribution of Beta Klotho Gene Expression in the Mouse Brain

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1959 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Bianca S Bono ◽

Persephone A Miller ◽

Nikita K Koziel Ly ◽

Melissa J Chee

Keyword(s):

Basolateral Amygdala ◽

Piriform Cortex ◽

Brain Regions ◽

Brain Atlas ◽

Hypothalamic Nucleus ◽

Fibroblast Growth Factor 21 ◽

Lateral Olfactory Tract ◽

Hypothalamic Area ◽

Low Levels ◽

The Brain

Abstract Fibroblast growth factor 21 (FGF21) has emerged as a critical endocrine factor for understanding the neurobiology of obesity, such as by the regulation thermogenesis, food preference, and metabolism, as well as for neuroprotection in Alzheimer’s disease and traumatic brain injury. FGF21 is synthesized primarily by the liver and pancreas then crosses the blood brain barrier to exert its effects in the brain. However, the sites of FGF21 action in the brain is not well-defined. FGF21 action requires the activation of FGF receptor 1c as well as its obligate co-receptor beta klotho (KLB). In order to determine the sites of FGF21 action, we mapped the distribution of Klb mRNA by in situ hybridization using RNAscope technology. We labeled Klb distribution throughout the rostrocaudal axis of male wildtype mice by amplifying Klb hybridization using tyramine signal amplification and visualizing Klb hybridization using Cyanine 3 fluorescence. The resulting Klb signal appears as punctate red “dots,” and each Klb neuron may express low (1–4 dots), medium (5–9 dots), or high levels (10+ dots) of Klb hybridization. We then mapped individual Klb expressing neuron to the atlas plates provided by the Allen Brain Atlas in order to determine Klb distribution within the substructures of each brain region, which are defined by Nissl-based parcellations of cytoarchitectural boundaries. The distribution of Klb mRNA is widespread throughout the brain, and the brain regions analyzed thus far point to notable expression in the hypothalamus, amygdala, hippocampus, and the cerebral cortex. The highest expression of Klb was localized to the suprachiasmatic nucleus in the hypothalamus, which contained low and medium Klb-expressing neurons in the lateral hypothalamic area and ventromedial hypothalamic nucleus while low expressing Klb neurons were seen in the paraventricular and dorsmedial hypothalamic nucleus. Hippocampal Klb expression was limited to the dorsal region and largely restricted to the pyramidal cell layer of the dentate gyrus, CA3, CA2, and CA1 but at low levels only. In the amygdala, low and medium Klb expressing cells were seen in lateral amygdala nucleus while low levels were observed in the basolateral amygdala nucleus. Cortical Klb expression analyzed thus far included low Klb-expressing neurons in the olfactory areas, including layers 2 and 3 of piriform cortex and nucleus of the lateral olfactory tract. These findings are consistent with the known roles of FGF21 in the central regulation of energy balance, but also implicates potentially wide-ranging effects of FGF21 such as in executive functions.

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