Tonic Enhancement of Endocannabinoid-Mediated Retrograde Suppression of Inhibition by Cholinergic Interneuron Activity in the Striatum

Being in the state of having both a strong impulse to act and a simultaneous need to withhold is commonly described as an “urge.” Although urges are part of everyday life and also important to several clinical disorders, the components of urge are poorly understood. It has been conjectured that withholding an action during urge involves active response suppression. We tested that idea by designing an urge paradigm that required participants to resist an impulse to press a button and gain relief from heat (one hand was poised to press while the other arm had heat stimulation). We first used paired-pulse TMS over motor cortex (M1) to measure corticospinal excitability of the hand that could press for relief, while participants withheld movement. We observed increased short-interval intracortical inhibition, an index of M1 GABAergic interneuron activity that was maintained across seconds and specific to the task-relevant finger. A second experiment replicated this. We next used EEG to better “image” putative cortical signatures of motor suppression and pain. We found increased sensorimotor beta contralateral to the task-relevant hand while participants withheld the movement during heat. We interpret this as further evidence of a motor suppressive process. Additionally, there was beta desynchronization contralateral to the arm with heat, which could reflect a pain signature. Strikingly, participants who “suppressed” more exhibited less of a putative “pain” response. We speculate that, during urge, a suppressive state may have functional relevance for both resisting a prohibited action and for mitigating discomfort.

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Effect of temperature on spontaneous interneuron activity in grasshoppers Tettigonia cantans and Metrioptera roeselii (Orthoptera, Tettigoniidae)

Journal of Evolutionary Biochemistry and Physiology ◽

10.1134/s0022093006060044 ◽

2006 ◽

Vol 42 (6) ◽

pp. 686-690 ◽

Cited By ~ 2

Author(s):

R. D. Zhantiev ◽

V. S. Chukanov ◽

O. S. Korsunovskaya

Keyword(s):

Effect Of Temperature ◽

Interneuron Activity

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Two Neuropeptides Colocalized in a Command-Like Neuron Use Distinct Mechanisms to Enhance Its Fast Synaptic Connection

Journal of Neurophysiology ◽

10.1152/jn.00358.2003 ◽

2003 ◽

Vol 90 (3) ◽

pp. 2074-2079 ◽

Cited By ~ 28

Author(s):

H.-Y. Koh ◽

F. S. Vilim ◽

J. Jing ◽

K. R. Weiss

Keyword(s):

High Frequency ◽

Synaptic Connection ◽

Quantal Content ◽

Functional Consequence ◽

Functional Implication ◽

Quantal Size ◽

Quantal Analysis ◽

Cholinergic Interneuron ◽

Single Synapse ◽

Stimulation Of

In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size ( q) and CP2 increases the calculated quantal content ( m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.

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Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer’s disease

Molecular Psychiatry ◽

10.1038/s41380-019-0483-4 ◽

2019 ◽

Vol 25 (12) ◽

pp. 3380-3398 ◽

Cited By ~ 15

Author(s):

Sara Hijazi ◽

Tim S. Heistek ◽

Philip Scheltens ◽

Ulf Neumann ◽

Derya R. Shimshek ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Neuronal Network ◽

Pyramidal Cells ◽

Network Activity ◽

Inhibitory Input ◽

Model Of Alzheimer’S Disease ◽

Entry Points ◽

Interneuron Activity

AbstractNeuronal network dysfunction is increasingly recognized as an early symptom in Alzheimer’s disease (AD) and may provide new entry points for diagnosis and intervention. Here, we show that amyloid-beta-induced hyperexcitability of hippocampal inhibitory parvalbumin (PV) interneurons importantly contributes to neuronal network dysfunction and memory impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We demonstrate that hippocampal PV interneurons become hyperexcitable at ~16 weeks of age, when no changes are observed yet in the intrinsic properties of pyramidal cells. This hyperexcitable state of PV interneurons coincides with increased inhibitory transmission onto hippocampal pyramidal neurons and deficits in spatial learning and memory. We show that treatment aimed at preventing PV interneurons from becoming hyperexcitable is sufficient to restore PV interneuron properties to wild-type levels, reduce inhibitory input onto pyramidal cells, and rescue memory deficits in APP/PS1 mice. Importantly, we demonstrate that early intervention aimed at restoring PV interneuron activity has long-term beneficial effects on memory and hippocampal network activity, and reduces amyloid plaque deposition, a hallmark of AD pathology. Taken together, these findings suggest that early treatment of PV interneuron hyperactivity might be clinically relevant in preventing memory decline and delaying AD progression.

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