title: Specific Targeting of the Basolateral Amygdala to Projectionally Defined Pyramidal Neurons in Prelimbic and Infralimbic Cortex.
abstract: Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal cortex have distinct roles in emotional learning. A complete mechanistic understanding underlying this dichotomy remains unclear. Here we explored targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a limbic structure pivotal in pain and fear processing. In mice, we used retrograde labeling, brain-slice recordings, and adenoviral optogenetics to dissect connectivity of ascending BLA input onto PL and IL neurons projecting to the periaqueductal gray (PAG) or the amygdala. We found differential targeting of BLA projections to PL and IL cortex. Activating BLA projections evoked excitatory and inhibitory responses in cortico-PAG (CP) neurons in layer 5 (L5) of both PL and IL cortex. However, all inhibitory responses were polysynaptic and monosynaptic BLA input was stronger to CP neurons in IL cortex. Conversely, the BLA preferentially targeted corticoamygdalar (CA) neurons in layer 2 (L2) of PL over IL cortex. We also reveal that BLA input is projection specific by showing preferential targeting of L5 CP neurons over neighboring L3/5 CA neurons in IL cortex. We conclude by showing that BLA input is laminar-specific by producing stronger excitatory responses CA neurons in L3/5 compared with L2 in IL cortex. Collectively, this study reveals differential targeting of the BLA to PL and IL cortex, which depends both on laminar location and projection target of cortical neurons. Overall, our findings should have important implications for understanding the processing of pain and fear input by the PL and IL cortex.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine-South Bend , South Bend, Indiana 46617.
authors.forename: John
authors.identifier: 0000-0001-8330-0866
authors.initials: J
authors.lastname: Cheriyan
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine-South Bend , South Bend, Indiana 46617.
authors.forename: Mahesh K
authors.identifier: 0000-0003-4286-1573
authors.initials: MK
authors.lastname: Kaushik
authors.affiliation: Department of Biological Sciences, University of Notre Dame , Notre Dame, Indiana 46556.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine-South Bend, South Bend, Indiana 46617; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556.
authors.forename: Patrick L
authors.identifier: 0000-0001-9630-2924
authors.initials: PL
authors.lastname: Sheets
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D066272:Basolateral Nuclear Complex / Q000502:physiology*; D000075402:Channelrhodopsins; D002772:Cholera Toxin / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008032:Limbic System / Q000166:cytology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D018698:Glutamic Acid; D002772:Cholera Toxin
keywords: basolateral amygdala; infralimbic; long-range connectivity; medial prefrontal cortex; periaqueductal gray; prelimbic