Voltammetric evidence for discrete serotonin circuits, linked to specific reuptake domains, in the mouse medial prefrontal cortex

Alyssa West, Janet Best, Aya Abdalla, H. Frederik Nijhout, Michael Reed, Parastoo Hashemi

Research output: Contribution to journalArticle

Abstract

The medial prefrontal cortex (mPFC) is an important brain region, that controls a variety of behavioral and functional outputs. As an important step in characterizing mPFC functionality, in this paper we focus on chemically defining serotonin transmission in this area. We apply cutting-edge analytical methods, fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption cyclic voltammetry (FSCAV), pioneered in our laboratory, for the first real-time in vivo analysis of serotonin in the mPFC. In prior in vivo work in the substantia nigra, pars reticulata, we found that our sub-second measurements of a single evoked serotonin release were subject to two clearance mechanisms. These mechanisms were readily modeled via Uptake 1, mediated by the serotonin transporters (SERTs), and Uptake 2, mediated by monoamine transporters (dopamine transporters (DATs), norepinephrine transporters (NETs), and organic cation transporters (OCTs)). Here in the mPFC, for the first time to our knowledge, we observe two release events in response to a single stimulation of the medial forebrain bundle (MFB). Of particular note is that each response is tied to a discrete reuptake profile comprising both Uptake 1 and 2. We hypothesize that two distinct populations of serotonin axons traverse the MFB and terminate in different domains with specific reuptake profiles. We test and confirm this hypothesis using a multifaceted pharmacological, histological and mathematical approach. We thus present evidence for a highly elaborate biochemical organization that regulates serotonin chemistry in the mPFC. This knowledge provides a solid foundation on which to base future studies of the involvement of the mPFC in brain function and behavior.

Original languageEnglish
Pages (from-to)50-58
Number of pages9
JournalNeurochemistry International
Volume123
DOIs
Publication statusPublished - 19 Jul 2018

Fingerprint

Prefrontal Cortex
Serotonin
Medial Forebrain Bundle
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Brain
Adsorption
Axons
Cations
Pharmacology
Population

Keywords

  • 6 max.) FSCV
  • Carbon fiber microelectrodes
  • MFB
  • Michaelis-menten
  • Uptake 1
  • Uptake 2

Cite this

West, Alyssa ; Best, Janet ; Abdalla, Aya ; Nijhout, H. Frederik ; Reed, Michael ; Hashemi, Parastoo. / Voltammetric evidence for discrete serotonin circuits, linked to specific reuptake domains, in the mouse medial prefrontal cortex. In: Neurochemistry International. 2018 ; Vol. 123. pp. 50-58.
@article{bb68910c970346fab91578ebf142b2cc,
title = "Voltammetric evidence for discrete serotonin circuits, linked to specific reuptake domains, in the mouse medial prefrontal cortex",
abstract = "The medial prefrontal cortex (mPFC) is an important brain region, that controls a variety of behavioral and functional outputs. As an important step in characterizing mPFC functionality, in this paper we focus on chemically defining serotonin transmission in this area. We apply cutting-edge analytical methods, fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption cyclic voltammetry (FSCAV), pioneered in our laboratory, for the first real-time in vivo analysis of serotonin in the mPFC. In prior in vivo work in the substantia nigra, pars reticulata, we found that our sub-second measurements of a single evoked serotonin release were subject to two clearance mechanisms. These mechanisms were readily modeled via Uptake 1, mediated by the serotonin transporters (SERTs), and Uptake 2, mediated by monoamine transporters (dopamine transporters (DATs), norepinephrine transporters (NETs), and organic cation transporters (OCTs)). Here in the mPFC, for the first time to our knowledge, we observe two release events in response to a single stimulation of the medial forebrain bundle (MFB). Of particular note is that each response is tied to a discrete reuptake profile comprising both Uptake 1 and 2. We hypothesize that two distinct populations of serotonin axons traverse the MFB and terminate in different domains with specific reuptake profiles. We test and confirm this hypothesis using a multifaceted pharmacological, histological and mathematical approach. We thus present evidence for a highly elaborate biochemical organization that regulates serotonin chemistry in the mPFC. This knowledge provides a solid foundation on which to base future studies of the involvement of the mPFC in brain function and behavior.",
keywords = "6 max.) FSCV, Carbon fiber microelectrodes, MFB, Michaelis-menten, Uptake 1, Uptake 2",
author = "Alyssa West and Janet Best and Aya Abdalla and Nijhout, {H. Frederik} and Michael Reed and Parastoo Hashemi",
year = "2018",
month = "7",
day = "19",
doi = "10.1016/j.neuint.2018.07.004",
language = "English",
volume = "123",
pages = "50--58",
journal = "Neurochemistry International",
issn = "0197-0186",

}

Voltammetric evidence for discrete serotonin circuits, linked to specific reuptake domains, in the mouse medial prefrontal cortex. / West, Alyssa; Best, Janet; Abdalla, Aya; Nijhout, H. Frederik; Reed, Michael; Hashemi, Parastoo.

In: Neurochemistry International, Vol. 123, 19.07.2018, p. 50-58.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Voltammetric evidence for discrete serotonin circuits, linked to specific reuptake domains, in the mouse medial prefrontal cortex

AU - West, Alyssa

AU - Best, Janet

AU - Abdalla, Aya

AU - Nijhout, H. Frederik

AU - Reed, Michael

AU - Hashemi, Parastoo

PY - 2018/7/19

Y1 - 2018/7/19

N2 - The medial prefrontal cortex (mPFC) is an important brain region, that controls a variety of behavioral and functional outputs. As an important step in characterizing mPFC functionality, in this paper we focus on chemically defining serotonin transmission in this area. We apply cutting-edge analytical methods, fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption cyclic voltammetry (FSCAV), pioneered in our laboratory, for the first real-time in vivo analysis of serotonin in the mPFC. In prior in vivo work in the substantia nigra, pars reticulata, we found that our sub-second measurements of a single evoked serotonin release were subject to two clearance mechanisms. These mechanisms were readily modeled via Uptake 1, mediated by the serotonin transporters (SERTs), and Uptake 2, mediated by monoamine transporters (dopamine transporters (DATs), norepinephrine transporters (NETs), and organic cation transporters (OCTs)). Here in the mPFC, for the first time to our knowledge, we observe two release events in response to a single stimulation of the medial forebrain bundle (MFB). Of particular note is that each response is tied to a discrete reuptake profile comprising both Uptake 1 and 2. We hypothesize that two distinct populations of serotonin axons traverse the MFB and terminate in different domains with specific reuptake profiles. We test and confirm this hypothesis using a multifaceted pharmacological, histological and mathematical approach. We thus present evidence for a highly elaborate biochemical organization that regulates serotonin chemistry in the mPFC. This knowledge provides a solid foundation on which to base future studies of the involvement of the mPFC in brain function and behavior.

AB - The medial prefrontal cortex (mPFC) is an important brain region, that controls a variety of behavioral and functional outputs. As an important step in characterizing mPFC functionality, in this paper we focus on chemically defining serotonin transmission in this area. We apply cutting-edge analytical methods, fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption cyclic voltammetry (FSCAV), pioneered in our laboratory, for the first real-time in vivo analysis of serotonin in the mPFC. In prior in vivo work in the substantia nigra, pars reticulata, we found that our sub-second measurements of a single evoked serotonin release were subject to two clearance mechanisms. These mechanisms were readily modeled via Uptake 1, mediated by the serotonin transporters (SERTs), and Uptake 2, mediated by monoamine transporters (dopamine transporters (DATs), norepinephrine transporters (NETs), and organic cation transporters (OCTs)). Here in the mPFC, for the first time to our knowledge, we observe two release events in response to a single stimulation of the medial forebrain bundle (MFB). Of particular note is that each response is tied to a discrete reuptake profile comprising both Uptake 1 and 2. We hypothesize that two distinct populations of serotonin axons traverse the MFB and terminate in different domains with specific reuptake profiles. We test and confirm this hypothesis using a multifaceted pharmacological, histological and mathematical approach. We thus present evidence for a highly elaborate biochemical organization that regulates serotonin chemistry in the mPFC. This knowledge provides a solid foundation on which to base future studies of the involvement of the mPFC in brain function and behavior.

KW - 6 max.) FSCV

KW - Carbon fiber microelectrodes

KW - MFB

KW - Michaelis-menten

KW - Uptake 1

KW - Uptake 2

UR - http://www.scopus.com/inward/record.url?scp=85051071031&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2018.07.004

DO - 10.1016/j.neuint.2018.07.004

M3 - Article

C2 - 30031052

AN - SCOPUS:85051071031

VL - 123

SP - 50

EP - 58

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

ER -