In Vitro Optogenetic Characterization of Neuropeptide Release from Prefrontal Cortical Somatostatin Neurons

Dao, Nigel C.; Brockway, Dakota F.; Crowley, Nicole A.

doi:10.1016/j.neuroscience.2019.08.014

Cited by 26 publications

(26 citation statements)

References 20 publications

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“…We injected SST-IRES-Cre male and female mice with the Cre-dependent viral construct encoding for the light-inducible channerhodopsin-2 (ChR2) in the PL ( Figure 3A ). Action potentials in ChR2+ SST neurons were elicited by 1-ms blue light (470 nm) photostimulation, with full action potential fidelity upward of 10 Hz ( Figure 3A ), consistent with SST firing patterns we have previously published (36). Next, we used a paired-pulse photostimulation protocol (2 x 1 ms pulses, 100 ms interval) to evoke release from SST neurons while recording from either pyramidal neurons or putatively GABAergic, non-SST neurons.…”

Section: Resultssupporting

confidence: 87%

Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

et al. 2020

Preprint

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Somatostatin neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance abuse disorders, including alcohol use disorder (AUD), is not fully characterized. Here we found that repeat cycles of alcohol binge drinking in the Drinking-in-the-Dark (DID) model led to hypoactivity of somatostatin (SST) neuronal in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons paradoxically reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. This effect is mediated directly via monosynaptic connection from SST neurons onto pyramidal neurons and indirectly via an intermediate GABAergic source. Optogenetic-assisted circuit mapping revealed that PL SST neurons preferentially synapse onto pyramidal neurons over other GABAergic populations in males, whereas SST neuron-mediated inhibition is balanced across cell types in females. Alcohol binge drinking disinhibits pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations. Together these data suggest substantial interaction between alcohol binge drinking and SST neurons inhibitory circuit in the PL, as well as provide evidence for these neurons as a potential therapeutic candidate for the treatment of alcohol use disorders, including binge drinking.

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Section: Resultssupporting

confidence: 87%

Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

et al. 2020

Preprint

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“…One interpretation is that CCK like other neuropeptides is released from STC apical dendritic terminals by an extremely small quantity (van den Pol, 2012) to produce a small and slow depolarization in SAC dendritic terminals that might not be detectable at SAC somata. Future work may be needed to directly measure CCK release in response to optogenetic activation of CCKergic TCs with the sensitive enzyme immunoassay (Dao et al, 2019).…”

Section: Cckergic Tcs Drive Inhibitory Glomerular Interneuronsmentioning

confidence: 99%

CCKergic Tufted Cells Differentially Drive Two Anatomically Segregated Inhibitory Circuits in the Mouse Olfactory Bulb

et al. 2020

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Delineation of functional synaptic connections is fundamental to understanding sensory processing. Olfactory signals are synaptically processed initially in the olfactory bulb (OB) where neural circuits are formed among inhibitory interneurons and the output neurons mitral cells (MCs) and tufted cells (TCs). TCs function in parallel with but differently from MCs and are further classified into multiple subpopulations based on their anatomic and functional heterogeneities. Here, we combined optogenetics with electrophysiology to characterize the synaptic transmission from a subpopulation of TCs, which exclusively express the neuropeptide cholecystokinin (CCK), to two groups of spatially segregated GABAergic interneurons, granule cells (GCs) and glomerular interneurons in mice of both sexes with four major findings. First, CCKergic TCs receive direct input from the olfactory sensory neurons (OSNs). This monosynaptic transmission exhibits high fidelity in response to repetitive OSN input. Second, CCKergic TCs drive GCs through two functionally distinct types of monosynaptic connections: (1) dendrodendritic synapses onto GC distal dendrites via their lateral dendrites in the superficial external plexiform layer (EPL); (2) axodendritic synapses onto GC proximal dendrites via their axon collaterals or terminals in the internal plexiform layer (IPL) on both sides of each bulb. Third, CCKergic TCs monosynaptically excite two subpopulations of inhibitory glomerular interneurons via dendrodendritic synapses. Finally, sniff-like patterned activation of CCKergic TCs induces robust frequency-dependent depression of the dendrodendritic synapses but facilitation of the axodendritic synapses. These results demonstrated important roles of the CCKergic TCs in olfactory processing by orchestrating OB inhibitory activities.

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“…Also, some GABA/peptidergic neurons are thought to express multiple peptides, and it is unclear under what conditions these individual (and sometimes functionally opposing) peptides are released. Despite these challenges in studying neuropeptides, recent technological advances have made it easier to investigate peptidergic transmission in various brain regions (Al-Hasani et al, 2015Crowley et al, 2016), including detecting neuropeptide release within the PFC (Dao et al, 2019).…”

Section: Peptide Populations Within the Prefrontal Cortexmentioning

confidence: 99%

“…SST expression is often used to classify inhibitory GABAergic neurons which mainly synapse on the dendrites of pyramidal cells within the cortex (Melchitzky and Lewis, 2008), though they have also been shown to project onto other populations including inhibitory neurons in the PFC (Cummings and Clem, 2020). SST+ neurons in the PFC have been shown to release SST under basal or tonic conditions as well as following activation (Dao et al, 2019); therefore, changes in the number or activity of SST cells in the PFC may not only result in altered GABAergic signaling but also altered SST tone. The GABAergic properties of SST cells in the cortex are known to control network activity, and the implications of SST-specific GABAergic dysfunction on neuropsychiatric disorders have been previously reviewed (Liguz-Lecznar et al, 2016;Urban-Ciecko and Barth, 2016;Robinson and Thiele, 2020).…”

Section: Somatostatin (Sst) Sst Neuropeptide Signaling and Overall Actionsmentioning

confidence: 99%

“…Results concerning the action of SST on neuronal activity are sparse, and very few experiments have been conducted in the PFC. SST+ neurons in the PFC have been shown to release somatostatin in an activity dependent manner (Dao et al, 2019), and dopamine can stimulate cortical SST release (Thal et al, 1986). The release of SST in the PFC indicates that it likely functions as an important neuromodulator in this region.…”

Section: Somatostatin (Sst) Sst Neuropeptide Signaling and Overall Actionsmentioning

confidence: 99%

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Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex

Brockway

Crowley

2020

Front. Behav. Neurosci.

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Recent advancements in technology have enabled researchers to probe the brain with the greater region, cell, and receptor specificity. These developments have allowed for a more thorough understanding of how regulation of the neurophysiology within a region is essential for maintaining healthy brain function. Stress has been shown to alter the prefrontal cortex (PFC) functioning, and evidence links functional impairments in PFC brain activity with neuropsychiatric disorders. Moreover, a growing body of literature highlights the importance of neuropeptides in the PFC to modulate neural signaling and to influence behavior. The converging evidence outlined in this review indicates that neuropeptides in the PFC are specifically impacted by stress, and are found to be dysregulated in numerous stress-related neuropsychiatric disorders including substance use disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia. This review explores how neuropeptides in the PFC function to regulate the neural activity, and how genetic and environmental factors, such as stress, lead to dysregulation in neuropeptide systems, which may ultimately contribute to the pathology of neuropsychiatric diseases.

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In Vitro Optogenetic Characterization of Neuropeptide Release from Prefrontal Cortical Somatostatin Neurons

Cited by 26 publications

References 20 publications

Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

CCKergic Tufted Cells Differentially Drive Two Anatomically Segregated Inhibitory Circuits in the Mouse Olfactory Bulb

Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex

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