Kedo O, Zilles K, Palomero-Gallagher N, Amunts K (2018) Mapping of M2 and 5-HT1A Receptors in the Human Amygdala. Clin Med Img Lib 4:105.

IMAGE ARTICLE | OPEN ACCESS DOI: 10.23937/2474-3682/1510105

Mapping of M2 and 5-HT1A Receptors in the Human Amygdala

Olga Kedo1*, Karl Zilles1,2,3, Nicola Palomero-Gallagher1 and Katrin Amunts1,2,4

1Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany

2JARA-BRAIN, Jülich-Aachen Research Alliance, Germany

3Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany

4Cécile and Oskar Vogt Institute of Brain Research, Heinrich-Heine-University Düsseldorf, Germany


Human amygdala, Receptor architecture, Parcellation of the human amygdala

The human amygdala is a region involved in processing of emotions, especially fear. Moreover, the amygdala is implicated in facilitation of memory by emotional arousal [3]. The expression of neurotransmitter receptors is important for signal processing (excitation, inhibition, and modulation). For instance, activation of cholinergic muscarinic M1 and M2 receptors is required for modulation of memory consolidation within the basolateral nucleus [4]. Both cholinergic and serotoninergic neurotransmission modulates the inhibitory tonus in the basolateral nucleus, whereas disturbance in a balance of the network activity could lead to or accompany neurodevelopmental and neurodegenerative diseases [5]. In epilepsy, abnormal expression of multiple receptors (including higher M2 receptor and lower 5-HT1A receptor densities than in controls) was reported in the lateral nucleus of the amygdala [6].

Here, we demonstrate the distribution of cholinergic M2 and serotoninergic 5-HT1A receptors in subdivisions of the human amygdala as an example of the chemoarchitectonically heterogeneous organization of the amygdala (Figure 1). The individual subdivisions of the amygdala show distinct connectivities and functions in animal studies [7,8], but such data lack in humans. Therefore, the analysis of the expression of different receptors in individual subdivisions of the amygdala is of high functional relevance. E.g., the serotoninergic system is associated with anxiety: Serotonin 5-HT1A receptors reduce anxiety-like behavior after application of paroxetine [9]. 5-HT1A receptor-knockout mice showed heightened anxiety level [10], whereas anxious non-human primates (marmosets) showed reduced serotonin levels in the amygdala [11]. An fMRI study demonstrates that the superficial amygdala was associated with processing of social stimuli in humans [12]. This correlates with high densities of 5-HT1A receptors in this group of the amygdala (Figure 1, AHi subdivision in its ventral part).


Figure 1: Distribution of Cholinergic M2 and Serotoninergic 5-HT1A Receptors in the Human Amygdala.

Subdivisions of the amygdala were identified in the color-coded receptor autoradiographs immediately adjacent to Nissl-stained sections in the right hemisphere at the level of the central nucleus. Color scales visualize the concentrations for each receptor (cholinergic muscarinic M2 or serotoninergic 5-HT1A receptors). After incubation of 20-μm thick coronal sections with the respective tritium-labelled ligand and exposition of the sections against the tritium-sensitive films, the films were developed, digitized and transformed into the binding site concentrations (fmol/mg protein) by using a nonlinear calibration curve between co-exposed plastic [3H]-standards of a known, step-wise increasing radioactivity and the gray values of the actual autoradiograph [1].

Amygdaloid subdivisions (mapping is based on the parcellation scheme of the previous study [2]: AHi - amygdalohippocampal transition area (from the superficial amygdaloid group), Bm - basomedial nucleus, BL - basolateral nucleus, La - lateral nucleus, PL - paralaminar nucleus (constitute the laterobasal group), Me - medial nucleus, Ce - central nucleus (constituents of the centromedial group, classification from [2]).

Parts of the subdivisions: CM - caudomedial, D - dorsal, DL - dorsolateral, DM - dorsomedial, L - lateral, M - medial, I - intermediate, V - ventral, VL - ventrolateral, VM - ventromedial. Adjacent structures: AStr - amygdalostriatal transition area, Str - striatum, HATA - hippocampal-amygdaloid transition area, Hipp - hippocampus, SUB - subicular complex, Ent - entorhinal cortex.


  1. Zilles K, Schleicher A, Palomero-Gallagher N, Amunts K (2002) Quantitative Analysis of Cyto- and Receptor Architecture of the Human Brain. In: Mazziotta JC, Toga AW, Brain Mapping: The Methods. Elsevier, (2nd edn), Amsterdam, 573-602.
  2. Kedo O, Zilles K, Palomero-Gallagher N, Schleicher A, Mohlberg H, et al. (2018) Receptor-driven, multimodal mapping of the human amygdala. Brain Struct Funct 223: 1637-1666.
  3. McGaugh JL (2002) Memory consolidation and the amygdala: A systems perspective. Trends Neurosci 25: 456.
  4. Power AE, McIntyre CK, Litmanovich A, Mc Gaugh JL (2003) Cholinergic modulation of memory in the basolateral amygdala involves activation of both m1 and m2 receptors. Behav Pharmacol 14: 207-213.
  5. Prager EM, Bergstrom HC, Wynn GH, Braga MF (2015) The basolateral amygdala gamma-aminobutyric acidergic system in health and disease. J Neurosci Res 94: 548-567.
  6. Graebenitz S, Kedo O, Speckmann EJ, Gorji A, Panneck H, et al. (2011) Interictal-like network activity and receptor expression in the epileptic human lateral amygdala. Brain 134: 2929-2947.
  7. Lalumiere RT (2014) Optogenetic dissection of amygdala functioning. Front Behav Neurosci 8: 1-7.
  8. Stefanacci L, Amaral DG (2002) Some observations on cortical inputs to the macaque monkey amygdala: An anterograde tracing study. J Comp Neurol 451: 301-323.
  9. Kõks S, Beljajev S, Koovit I, Abramov U, Bourin M, et al. (2001) 8-OH-DPAT, but not deramciclane, antagonizes the anxiogenic-like action of paroxetine in an elevated plus-maze. Psychopharmacol 153: 365-372.
  10. Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, et al. (1998) Serotonin receptor 1A knockout: An animal model of anxiety-related disorder. Proc Natl Acad Sci U S A 95: 14476-14481.
  11. Mikheenko Y, Shiba Y, Sawiak S, Braesicke K, Cockcroft G, et al. (2015) Serotonergic, brain volume and attentional correlates of trait anxiety in primates. Neuropsychopharmacology 40: 1395-1404.
  12. Goossens L, Kukolja J, Onur OA, Fink GR, Maier W, et al. (2009) Selective processing of social stimuli in the superficial amygdala. Hum Brain Mapp 30: 3332-3338.


Kedo O, Zilles K, Palomero-Gallagher N, Amunts K (2018) Mapping of M2 and 5-HT1A Receptors in the Human Amygdala. Clin Med Img Lib 4:105.