Sensory/ Motor Systems March 24, 2011 Greg Suh greg.suh@med.nyu.edu Title: Chemical Senses-­‐ central In last lecture, we covered: 1.  Olfactory sensory system in mammals, flies, worms 2.  Vomeronasal sensory system in mammals 3.  Taste sensory system in mammals The Main Olfactory System 4 Both the MOE and VNO detect pheromonal ligands at low concentra9ons. a, b, Electrophysiological recordings from wild-­‐type (WT) and gene-­‐targeted mice showing examples of field-­‐poten9al responses to the same pheromone ligands at low concentra9ons (10-­‐10 M) in the MOE and VNO. 2-­‐Heptanone is a urinary cons9tuent that has a primer pheromonal effect, extending the length of female oestrous cycles18. SYFPEITHI is a prototypical MHC class-­‐I pep9de ligand (for the H-­‐2d haplotype of BALB/c mice). Note that both MOE responses are absent in mice with a targeted muta9on in the cyclic-­‐nucleo9de-­‐gated channel subunit CNGA2. The response to 2-­‐heptanone is absent in the VNO of mice with a targeted muta9on in the transient-­‐receptor-­‐poten9al channel TRPC2; however, the response to SYFPEITHI is rela9vely normal in these mutants. c–e, Large-­‐scale confocal Ca2+ imaging with cellular resolu9on using a nasal coronal 9ssue slice iden9fies discrete popula9ons of pep9de-­‐
detec9ng olfactory sensory neurons in the mouse MOE. AAPDNRETF is a prototypical MHC class-­‐I pep9de ligand for the H-­‐2b haplotype of C57BL/6 mice. A por9on of the olfactory epithelium delimited by the white box in c is shown at higher magnifica9on in d and e. d, Confocal fluorescence image of the fluo-­‐4-­‐loaded olfactory epithelium acquired at rest (grayscale). e, Pseudocolour image of the rela9ve increase in pep9de-­‐induced Ca2+ fluorescence, showing four responsive OSNs. S, septal wall; DR, dorsal recess; I, endoturbinate I. Pheromonal communica9on in vertebrates Peter A. Brennan and Frank Zufall Nature 444, 308-­‐315(16 November 2006) Schema9c diagram of central olfactory pathways (KSJ 32-­‐9). 8 Schema9c diagram of central olfactory pathways (KSJ 32-­‐9). The medial amygdala is an important hub that controls social behaviour. The medial amygdala (MeA) receives input from both the vomeronasal structures (red) and main olfactory structures (blue), and is a major site for the integra9on of chemosensory informa9on with other sensory cues and hormonal states. The MeA elicits behavioural, endocrine and autonomic responses to pheromones through its output to the hypothalamus and central nucleus of the amygdala (CEA). Projec9ons to the basolateral nuclei of the amygdala (BLA) and nucleus accumbens are likely to be involved in learned behavioural responses to condi9oned s9muli. Interconnec9ons of the individual structures not involving the MeA have been omiied for clarity. The central projec9ons and possible integra9on sites from the septal organ of Masera, the Grueneberg ganglion and the GCD-­‐cell system are unclear. ACo, anterior cor9cal amygdala; AON, anterior olfactory nucleus; BAOT, bed nucleus of the accessory olfactory tract; BNST, bed nucleus of the stria terminalis; NLOT, nucleus of the lateral olfactory tract; PIR, piriform cortex; PLCo, posterior lateral cor9cal amygdala; PMCo, posterior medial cor9cal amygdala. This simplified version of the connec9vity of the MeA is based on neuroanatomical data from rats. Pheromonal communica9on in vertebrates Peter A. Brennan and Frank Zufall Nature 444, 308-­‐315(16 November 2006) A lovely story about the connec9ons of the olfactory bulb with piriform cortex, from Buck’s Nobel Lecture ... OOPS! Figure 1: Odour images in the olfactory glomerular layer. a, Diagram showing the rela9onship between the olfactory receptor cell sheet in the nose and the glomeruli of the olfactory bulb53. b, fMRI images of the different but overlapping ac9vity paierns seen in the glomerular layer of the olfactory bulb of a mouse exposed to members of the straight-­‐chain aldehyde series, varying from four to six carbon atoms. The lower part of the image in the lem panel corresponds to the image on the medial side of the olfactory glomerular layer as shown in a (see asterisk). Smell images and the flavour system in the human brain Gordon M. Shepherd Nature 444, 316-­‐321(16 November 2006) The Bruce effect, one of the best-­‐known examples of olfactory imprin9ng in adult vertebrates. Urine from unfamiliar males (yellow) — or familiar urine (blue) supplemented with unfamiliar (disparate) MHC class-­‐1 pep9de ligands — ac9vates neuroendocrine mechanisms leading to pregnancy failure (a, b) by means of the AOB, amygdala and medial hypothalamus (c). The mated female learns to recognize the pheromones of the ma9ng male during a sensi9ve period around ma9ng. Subsequent exposure to her mate's urine ac9vates mitral cells (M) in the AOB that are subject to enhanced inhibi9on from granule cell (G) interneurons. This increased inhibi9on is thought to disrupt the transmission of the mate's pheromonal signal to the amygdala, preven9ng pregnancy block. Pheromonal communica9on in vertebrates Peter A. Brennan and Frank Zufall Nature 444, 308-­‐315(16 November 2006) The olfactory bulb receives signals from olfactory sensory neurons (KSJ 32-­‐7). Each sensory axon terminates in a single glomerulus, forming synapses with the dendrites of periglomerular interneurons, and mitral and tumed relay neurons. Within each glomerulus, periglomerular cells form inhibitory dendro-­‐dendri9c synapses with mitral cell dendrites. Granule cells form a second system of inhibitory neurons, through dendri9c interac9ons with relay neurons. Sensory informaIon is faithfully transferred to 2nd order PNs. By GCaMP imaging….. Wang et al. Nature 2004
2nd order PNs are broadly tuned to odorants.
By e-­‐phys recordings…. Wilson et al. Science 2004
CorrelaIon between imaging and e-­‐phys. Root C M et al. PNAS 2007;104:11826-11831
©2007 by National Academy of Sciences
Unconnected PNs get acIvated thru eLN….. But acIvaIon of unconnected PNs is not transferred. Projec9on Neurons Connect the Antennal Lobe to the Mushroom Body and Lateral Horn. 27 Expression of CD2 in a Popula9on of Projec9on Neurons 28 Expression of CD8-­‐GFP in Single Projec9on Neurons 29 Individual Projec9on Neurons Innervate a Single Glomerulus 30 Different Projec9on Neurons Show Dis9nct Paierns in the lateral horn. 31 Similari9es of Projec9on Paierns Lack of Obvious FuncIonal Replicates among 3rd ordered mushroom body neurons Fig. 4. Synchronized oscillatory discharges of mitral and tumed cells and presump9ve combina9on-­‐detec9ng neurons in the olfactory cortex. (Lem) The schema9c diagram of the olfactory bulb shows three glomerular modules (cells A through C) represen9ng three different odorant receptors. The traces under the diagram indicate the local field poten9al in the MOB (top trace), spike discharges of mitral cell A (green) (middle trace) and spike discharges of mitral cell B (orange) (boiom trace). Spike discharges are synchronized between cells A and B. (Right) Diagram of the olfactory cortex indicates presump9ve convergence of mitral cell axons onto individual cor9cal neurons. The traces indicate oscillatory local field poten9al in the olfactory cortex (top trace), synap9c and spike poten9als in the hypothe9cal cor9cal neuron (A + B) when the inputs are synchronized (middle trace), and synap9c poten9als when the inputs are unsynchronized (boiom trace). In the middle trace, temporal summa9on of synap9c inputs from mitral cells A and B gives rise to spike Mori K, Nagao H, Yoshihara Y (1999). The olfactory discharges of this cor9cal neuron. Bulb: coding and processing of odor molecule informa9on. Science 286:711-­‐715. Central gustatory pathways Central gustatory pathways Figure 3: The human brain flavour systems that evaluate and regulate food intake. The diagram shows the areas involved in the perceptual, emo9onal, memory-­‐related, mo9va9onal and linguis9c aspects of food evalua9on mediated by flavour inputs32, 41, 54, 55. Lem, different sensory modali9es and submodali9es that contribute to flavour percep9on. Middle and right, brain flavour system that evaluates and regulates food intake. Red regions mediate conscious sensory percep9on; thicker outlines indicate their greater importance in humans and other primates. Green regions mediate subconscious feeding regula9on. Deficiencies in essen9al amino acids are sensed by the anterior olfactory cortex (asterisk). Smell images and the flavour system in the human brain Gordon M. Shepherd Nature 444, 316-­‐321(16 November 2006) Smell images and the flavour system in the human brain Gordon M. Shepherd Nature 444, 316-­‐321(16 November 2006) Figure 1. Basic circuit diagram summarizing the synap9c organiza9on of the mammalian MOB. Two glomerular modules (brown and blue) represent two different types of odorant receptors. Mitral cells (M) and tumed cells (T) are output neurons, and granule cells (Gr) and periglomerular cells (PG) are local interneurons. OSN, olfactory sensory neuron; GL, glomerulus. Short white arrows denote excitatory synapses, and short black arrows denote inhibitory synapses. Mori K, Nagao H, Yoshihara Y (1999). The olfactory Bulb: coding and processing of odor molecule informa9on. Science 286:711-­‐715. Figure 2: The dual olfactory system. a, Brain systems involved in smell percep9on during orthonasal olfac9on (sniffing in). b, Brain systems involved in smell percep9on during retronasal olfac9on (breathing out), with food in the oral cavity. Air flows indicated by dashed and doied lines; doied lines indicate air carrying odour molecules. ACC, accumbens; AM, amygdala; AVI, anterior ventral insular cortex; DI, dorsal insular cortex; LH, lateral hypothalamus; LOFC, lateral orbitofrontal cortex; MOFC, medial orbitofrontal cortex; NST, nucleus of the solitary tract; OB, olfactory bulb; OC, olfactory cortex; OE, olfactory epithelium; PPC, posterior parietal cortex; SOM, somatosensory cortex; V, VII, IX, X, cranial nerves; VC, primary visual cortex; VPM, ventral posteromedial thalamic nucleus. Smell images and the flavour system in the human brain Gordon M. Shepherd Nature 444, 316-­‐321(16 November 2006)