Activity-dependent serotonergic excitation of callosal projection neurons in the mouse prefrontal cortex

Stephens, Emily K.; Avesar, Daniel; Gulledge, Allan T.

doi:10.3389/fncir.2014.00097

Cited by 31 publications

(55 citation statements)

References 88 publications

(143 reference statements)

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“…For instance, mouse COM neurons express G q ‐coupled 5‐HT 2A receptors in addition to mAChRs (Avesar & Gulledge, ; Stephens et al . ), but while 5‐HT triggers excitatory responses in COM neurons that are similar in magnitude to those evoked by ACh, and appear to be mediated by identical ionic mechanisms (Stephens et al . ), serotonergic SK‐mediated inhibition is absent (Avesar & Gulledge, ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, serotonin (5‐HT) inhibits CPn neurons via G i/o ‐coupled 5‐HT1A receptors, while selectively exciting COM neurons via activation of G q ‐coupled 5‐HT 2A receptors (Avesar & Gulledge, ; Stephens et al . , ). On the other hand, CPn neurons are preferentially excited by α2‐adrenergic (Dembrow et al .…”

Section: Introductionmentioning

confidence: 99%

“…In addition to having distinct morphological and physiological properties (Morishima & Kawaguchi, 2006;Dembrow et al 2010), CPn and COM neurons differ in their responses to neuromodulatory input (Dembrow & Johnston, 2014). For example, serotonin (5-HT) inhibits CPn neurons via G i/o -coupled 5-HT1A receptors, while selectively exciting COM neurons via activation of G q -coupled 5-HT 2A receptors (Avesar & Gulledge, 2012;Stephens et al 2014Stephens et al , 2018. On the other hand, CPn neurons are preferentially excited by α2-adrenergic (Dembrow et al 2010) and dopamine D2 (Gee et al 2012) receptors, while COM neurons are preferentially excited via activation of dopamine D1 receptors (Seong & Carter, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Preferential cholinergic excitation of corticopontine neurons

Baker

O’Toole

Gulledge

2018

The Journal of Physiology

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Pyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non-overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making and behaviour. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh). To better understand how ACh regulates cortical output, in slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron subtypes, exogenous ACh generated qualitatively similar biphasic responses in which brief hyperpolarization was followed by longer lasting enhancement of excitability. However, cholinergic inhibition was more pronounced in COM neurons, while excitatory responses were larger and longer lasting in CPn neurons. Similarly, optically triggered release of endogenous ACh from cholinergic terminals preferentially and persistently (for ∼40 s) enhanced the excitability of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of CPn neurons involved at least three distinct ionic mechanisms: suppression of K 7 channels (the 'M-current'), activation of the calcium-dependent non-specific cation conductance underlying afterdepolarizations, and activation of what appears to be a calcium-sensitive but calcium-permeable non-specific cation conductance. Our findings demonstrate projection-specific selectivity in cholinergic signalling in the PFC, and suggest that transient release of ACh during behaviour will preferentially promote corticofugal output.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preferential cholinergic excitation of corticopontine neurons

Baker

O’Toole

Gulledge

2018

The Journal of Physiology

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“…In the mPFC, postsynaptic serotonin receptors are differentially expressed by various subtypes of layer V pyramidal neurons that project to different targets (Avesar and Gulledge, 2012; Stephens et al, 2014). Thus, serotonin is well poised to dynamically regulate the flow of information both into and out of the mPFC, thereby coordinating its participation in distributed brain networks.…”

Section: Discussionmentioning

confidence: 99%

Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

et al. 2016

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SUMMARY Both the medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety, however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency (4–12 Hz) mPFC activity, and also reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function including anxiety-related behaviors.

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“…These two receptors show substantial colocalization in L6 pyramidal neurons in mPFC of mouse (Table 3 in Amargós-Bosch et al, 2004), yet typically appear to exert opposing electrophysiological effects in other cortical layers (Benekareddy et al, 2010; Avesar and Gulledge, 2012; Stephens et al, 2014). Whereas 5-HT 1A receptors are known inhibitory receptors acting via Kir3 channels (Goodfellow et al, 2014; Johnston et al, 2014), 5-HT 2A receptors act through a less well-characterized set of channels to excite certain populations of neurons, including a subset of L5 pyramidal neurons in mPFC (Willins et al, 1999; Benekareddy et al, 2010; Weber and Andrade, 2010; Avesar and Gulledge, 2012).…”

Section: Discussionmentioning

confidence: 99%