PMID- 38099294
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240219
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 11
DP  - 2023
TI  - Harnessing axonal transport to map reward circuitry: Differing brain-wide 
      projections from medial prefrontal cortical domains.
PG  - 1278831
LID - 10.3389/fcell.2023.1278831 [doi]
LID - 1278831
AB  - Neurons project long axons that contact other distant neurons. Neurons in the 
      medial prefrontal cortex project into the limbic system to regulate responses to 
      reward or threat. Diminished neural activity in prefrontal cortex is associated 
      with loss of executive function leading to drug use, yet the specific circuitry 
      that mediate these effects is unknown. Different regions within the medial 
      prefrontal cortex may project to differing limbic system nuclei. Here, we 
      exploited the cell biology of intracellular membrane trafficking, fast axonal 
      transport, to map projections from two adjacent medial prefrontal cortical 
      regions. We used Mn(II), a calcium analog, to trace medial prefrontal cortical 
      projections in the living animal by magnetic resonance imaging (MRI). Mn(II), a 
      contrast agent for MRI, enters neurons through voltage-activated calcium channels 
      and relies on kinesin-1 and amyloid-precursor protein to transport out axons to 
      distal destinations. Aqueous MnCl(2) together with fluorescent dextran (3--5 nL) 
      was stereotactically injected precisely into two adjacent regions of the medial 
      prefrontal cortex: anterior cingulate area (ACA) or infralimbic/prelimbic (IL/PL) 
      region. Projections were traced, first live by manganese-enhanced MRI (MEMRI) at 
      four time points in 3D, and then after fixation by microscopy. Data-driven 
      unbiased voxel-wise statistical maps of aligned normalized MR images after either 
      ACA or IL/PL injections revealed statistically significant progression of Mn(II) 
      over time into deeper brain regions: dorsal striatum, globus pallidus, amygdala, 
      hypothalamus, substantia nigra, dorsal raphe and locus coeruleus. Quantitative 
      comparisons of these distal accumulations at 24 h revealed dramatic differences 
      between ACA and IL/PL injection groups throughout the limbic system, and most 
      particularly in subdomains of the hypothalamus. ACA projections targeted 
      dorsomedial nucleus of the hypothalamus, posterior part of the periventricular 
      region and mammillary body nuclei as well as periaqueductal gray, while IL/PL 
      projections accumulated in anterior hypothalamic areas and lateral hypothalamic 
      nuclei as well as amygdala. As hypothalamic subsegments relay CNS activity to the 
      body, our results suggest new concepts about mind-body relationships and specific 
      roles of distinct yet adjacent medial prefrontal cortical segments. Our MR 
      imaging strategy, when applied to follow other cell biological processes in the 
      living organism, will undoubtedly lead to an expanded perspective on how minute 
      details of cellular processes influence whole body health and wellbeing.
CI  - Copyright (c) 2023 Bearer, Medina, Uselman and Jacobs.
FAU - Bearer, Elaine L
AU  - Bearer EL
AD  - Department of Pathology, University of New Mexico Health Sciences Center, 
      Albuquerque, NM, United States.
AD  - Division of Biology and Biological Engineering, California Institute of 
      Technology, Pasadena, CA, United States.
FAU - Medina, Christopher S
AU  - Medina CS
AD  - Department of Pathology, University of New Mexico Health Sciences Center, 
      Albuquerque, NM, United States.
FAU - Uselman, Taylor W
AU  - Uselman TW
AD  - Department of Pathology, University of New Mexico Health Sciences Center, 
      Albuquerque, NM, United States.
FAU - Jacobs, Russell E
AU  - Jacobs RE
AD  - Zilkha Neurogenetic Institute, USC Keck School of Medicine, Los Angeles, CA, 
      United States.
LA  - eng
GR  - P20 AG068077/AG/NIA NIH HHS/United States
GR  - R01 DA018184/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20231130
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
UOF - bioRxiv. 2023 Sep 10;:. PMID: 38328063
PMC - PMC10720719
OTO - NOTNLM
OT  - amygdala
OT  - anterior cingulate area (ACA) and infralimbic-prelimbic cortex (IL/PL)
OT  - axonal transport
OT  - calcium analog
OT  - hypthalamus
OT  - manganese-enhanced magnetic resonance imaging (MEMRI)
OT  - medial prefrontal cortex (mPFC)
OT  - statistical parametric mapping (SPM)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The author EB declared that they were an editorial board 
      member of Frontiers, at the time of submission. This had no impact on the peer 
      review process and the final decision.
EDAT- 2023/12/15 06:42
MHDA- 2023/12/15 06:43
PMCR- 2023/01/01
CRDT- 2023/12/15 04:04
PHST- 2023/08/17 00:00 [received]
PHST- 2023/09/25 00:00 [accepted]
PHST- 2023/12/15 06:43 [medline]
PHST- 2023/12/15 06:42 [pubmed]
PHST- 2023/12/15 04:04 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 1278831 [pii]
AID - 10.3389/fcell.2023.1278831 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2023 Nov 30;11:1278831. doi: 10.3389/fcell.2023.1278831. 
      eCollection 2023.