PMID- 38328063
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240219
DP  - 2023 Sep 10
TI  - Harnessing axonal transport to map reward circuitry: Differing brain-wide 
      projections from medial forebrain domains.
LID - 2023.09.10.557059 [pii]
LID - 10.1101/2023.09.10.557059 [doi]
AB  - Neurons project long axons that contact other distant neurons. Projections can be 
      mapped by hijacking endogenous membrane trafficking machinery by introducing 
      tracers. To witness functional connections in living animals, we developed a 
      tracer detectible by magnetic resonance imaging (MRI), Mn(II). Mn(II) relies on 
      kinesin-1 and amyloid-precursor protein to travel out axons. Within 24h, 
      projection fields of cortical neurons can be mapped brain-wide with this 
      technology. MnCl(2) was stereotactically injected either into anterior cingulate 
      area (ACA) or into infralimbic/prelimbic (IL/PL) of medial forebrain (n=10-12). 
      Projections were imaged, first by manganese-enhanced MRI (MEMRI) live, and then 
      after fixation by microscopy. MR images were collected at 100mum isotropic 
      resolution (~5 neurons) in 3D at four time points: before and at successive time 
      points after injections. Images were preprocessed by masking non-brain tissue, 
      followed by intensity scaling and spatial alignment. Actual injection locations, 
      measured from post-injection MR images, were found to be 0.06, 0.49 and 0.84mm 
      apart between cohorts, in R-L, A-P, and D-V directions respectively. Mn(II) 
      enhancements arrived in hindbrains by 24h in both cohorts, while co-injected 
      rhodamine dextran was not detectible beyond immediate subcortical projections. 
      Data-driven unbiased voxel-wise statistical maps after ACA injections revealed 
      significant progression of Mn(II) distally into deeper brain regions: globus 
      pallidus, dorsal striatum, amygdala, hypothalamus, substantia nigra, dorsal raphe 
      and locus coeruleus. Accumulation was quantified as a fraction of total volume of 
      each segment containing significantly enhanced voxels (fractional accumulation 
      volumes), and results visualized in column graphs. Unpaired t-tests between 
      groups of brain-wide voxel-wise intensity profiling by either region of interest 
      (ROI) measurements or statistical parametric mapping highlighted distinct 
      differences in distal accumulation between injection sites, with ACA projecting 
      to periaqueductal gray and IL/PL to basolateral amygdala (p<0.001 FDR). Mn(II) 
      distal accumulations differed dramatically between injection groups in subdomains 
      of the hypothalamus, with ACA targeting dorsal medial, periventricular region and 
      mammillary body nuclei, while IL/PL went to anterior hypothalamic areas and 
      lateral hypothalamic nuclei. Given that these hypothalamic subsegments 
      communicate activity in the central nervous system to the body, these 
      observations describing distinct forebrain projection fields will undoubtedly 
      lead to newer insights in mind-body relationships.
FAU - Bearer, E L
AU  - Bearer EL
AUID- ORCID: 0000-0002-8390-8529
AD  - Department of Pathology, Univ. of New Mexico Health Sciences Center, Albuquerque, 
      NM.
AD  - Division of Biology and Biological Engineering, California Institute of 
      Technology, Pasadena, CA.
FAU - Medina, C S
AU  - Medina CS
AD  - Department of Pathology, Univ. of New Mexico Health Sciences Center, Albuquerque, 
      NM.
FAU - Uselman, T W
AU  - Uselman TW
AUID- ORCID: 0000-0002-3856-5248
AD  - Department of Pathology, Univ. of New Mexico Health Sciences Center, Albuquerque, 
      NM.
FAU - Jacobs, R E
AU  - Jacobs RE
AUID- ORCID: 0000-0002-1382-8486
AD  - Zilkha Neurogenetic Institute, USC Keck School of Medicine, Los Angeles, CA.
LA  - eng
GR  - R01 DA018184/DA/NIDA NIH HHS/United States
GR  - R01 MH096093/MH/NIMH NIH HHS/United States
PT  - Preprint
DEP - 20230910
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - Front Cell Dev Biol. 2023 Nov 30;11:1278831. PMID: 38099294
PMC - PMC10849663
OTO - NOTNLM
OT  - Axonal transport
OT  - amygdala
OT  - anterior cingulate area (ACA) and infralimbic-prelimbic cortex (IL/PL)
OT  - computational image analysis
OT  - hypthalamus
OT  - manganese-enhanced magnetic resonance imaging (MEMRI)
OT  - medial prefrontal cortex (mPFC)
OT  - statistical parametric mapping (SPM)
EDAT- 2024/02/08 06:43
MHDA- 2024/02/08 06:44
PMCR- 2024/02/07
CRDT- 2024/02/08 04:15
PHST- 2024/02/08 06:43 [pubmed]
PHST- 2024/02/08 06:44 [medline]
PHST- 2024/02/08 04:15 [entrez]
PHST- 2024/02/07 00:00 [pmc-release]
AID - 2023.09.10.557059 [pii]
AID - 10.1101/2023.09.10.557059 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Sep 10:2023.09.10.557059. doi: 
      10.1101/2023.09.10.557059.