Sensory coding and somatosensory system

Transcription

1 Sensory coding and somatosensory system

2

3 Sensation and perception Perception is the internal construction of sensation. Perception depends on the individual experience.

4 Three common steps in all senses 1. A physical stimulus 2. A set of event transforming the stimulus into nerve impulses 3. A response to this signal in the form of a perception or conscious experience of sensation

5 Perception differs qualitatively from the physical properties of stimuli Nervous system extracts only certain pieces of information from each stimulus to interpret in the context of the brain s intrinsic structure and previous experiences. To receive - To perceive

6 Perception organizes the object s essential properties well enough to let us handle the object appropriately.

7 Four basic types of information Modality Intensity Location Timing

8 Modality To define a general class of stimulus Types of receptors Type of energy transmitted by the stimulus The receptor specialized to sense the energy Central pathway and target area in the brain

9 Location Position in space and its size The set of activated sensory receptors within the sensory system, which are distributed topographically.

10 Intensity The response amplitude of each receptor Timing When the response in the receptor starts and stops

11 Sensory receptor To transform specific types of stimulus energy into electrical energy (receptor potential) and electrical signal Receptor specificity Most receptors are optimally selective for a single stimulus energy (labeled line codes) Each receptor responds to a narrow range of stimulus energy Mechanical Chemical Thermal Electromagnetic

12 The spatial distribution of sensory neurons activated by a stimulus conveys information about the stimulus location The spatial abilities are linked to the structure of the receptive field of each sensory neuron. Each receptor responses only to stimulation within its receptive field. The density of receptors determines the resolution of detail of stimuli.

13 Sensory threshold for a modality is limited by receptor sensitivity Threshold energy The minimum stimulus amplitude that generates action potentials in a sensory nerve To convey a sensory message to the brain The stimulus information must be represented as a series of action potentials

14 Stimulus intensity is encoded by the frequency of action potentials in sensory nerves Strong stimuli Larger receptor potentials Greater number and a higher frequency of action potential

15 The duration of sensation is determined in part by the adaptation rates of receptors Adaptation If the stimulus persists for several minutes without a change in position or amplitude, its intensity diminished and sensation is lost. Slowly adapting receptors Rapidly adapting receptors

16 Common properties of sensory systems Each system responds specifically to a stimulus Constructs an orderly representation in CNS Separate lines of communication Spatial and temporal coding

17 General scheme of a sensory system Receptors Sensory neuron Spinal cord (or brain stem) Thalamus Cortex

18 Sensory systems process information in a series of relay nuclei Preprocess sensory information (convergence and filtering) Inhibition (feed-forward and feed-back contrast enhancing) Neurons in each sensory relay nucleus have a receptive field

19 Three inhibitory pathways in the circuitry of the dorsal column nuclei Sharpen contrast between stimuli A central zone of active neurons surrounded by a ring of less active neurons

20

21 Sensory cortex Primary and associate areas Common structure Columns and compartments Stereotype connections Areas in the same (ipsilateral) hemisphere Areas in the contralateral hemisphere Subcortical regions (focusing attention) Association areas perform broad functions

22 Sensory physiology To examine the neural consequences of a stimulus

23 Somatosensory system

24 Dorsal root ganglion neuron is the primary sensory neuron in the somatic sensory system Two principal functions 1. Stimulus transduction 2. Transmission of encoded stimulus information to CNS

25 Segmental organization of the spinal cord

26

27 Sensory organization of the spinal cord Dorsal horn Sensory function Ventral horn Motor function

28 Spinal cord cytoarchitecture Rexed scheme The gray matter is divided into 10 cytoarchitectonic regions, lamina I-IX, and an area around the central canal (area X).

29 Rexed s classification and important nuclei

30 Principal termination sites for afferent fibers from skin and muscle and viscera

31 o: outer i: inner Bd: the dorsalmost part of inner LII. Bv: most of inner LII.

32 Sensory receptors and the size of primary afferent axons

33 Conduction velocities of peripheral nerves

34 Types of dorsal root ganglion (DRG) neurons and their molecular markers Textbook of Pain IB4, isolectin B4 NF200, neurofilament 200 CGRP, calcitonin gene-related peptide

35 Termination of different types of primary afferent fibers in the dorsal horn of rat spinal cord

36 Distribution of the terminals of an individual cutaneous C fiber in the superficial dorsal horn

37

38 Many peripheral receptors converge onto a single sensory neuron in the central nervous system. The receptive field of a central sensory neuron may have a central excitatory receptive field surrounded by an inhibitory region.

39 Application of neuronal pathway tracing methods

40 Receptors of somatic sensation Mechanoreceptors Nociceptors Thermoreceptors Proprioceptors Chemoreceptors

41 Mechanoreceptors Touch is mediated by mechanoreceptors in the skin Principal mechanoreceptors Slowly adapting Rapidly adapting

42 Mechanoreceptors in the superficial and deep layers of skin have different receptive fields

43 Thermal receptors Cold receptor Warmth receptor Firing action potentials continuously at low rates

44 Thermoreceptors Warm receptor firing above 30 o C increase firing rate about 45 o C Cold receptor unresponsive above 35 o C fire faster over a broad range down to about 10 o C firing ceased below 10 o C could fire above 45 o C

45 Nociceptors Free, branching, unmyelinated nerve ending that signal the body tissue being damaged or at risk of being damaged. Mechanical nociceptor Thermal nociceptor > 45 o C, < 5 o C Polymodal nociceptor

46 Proprioceptors Proprioception is mediated by mechanoreceptors in skeletal muscle and joint capsules

47 Transient receptor potential (TRP) channels

48

49

50

51 TRP channels Temperature (C ) Noxious cold Noxious heat

52

53

54

55

56 Na + channels

57

58

59 Small DRG neurons expressing tyrosine hydroxylase (TH) function as C-LTMRs Li et al. (2011) Cell

60 Expression of the Mas1-related G-protein-coupled receptors (Mrgprs) in small DRG neurons Bader et al. (2014) Pharmacol. Rev.

61

62 Strategic Priority Research Program, Chinese Academy of Sciences Mapping Brain Functional Connections Neuron types and their neural circuits?

63 Single-neuron RNA-seq of DRG neurons High-coverage single-cell RNA-sequencing (10,950 ± 1,218 genes per neuron) Li et al. (2016) Cell Research

64 10 neuron clusters (C1 C10) and 14 subclusters 1,745 differentially expressed genes ( 5-fold change) from 197 neurons were used to analyze the neuronal clusters.

65 Molecular markers of neuron clusters and subclusters

66 Sensory functions of DRG neuron clusters Nxph1 encodes neurexophilin 1

67 Sensory functions of DRG neuron clusters Small neurons Large neurons

68 10 neuron types (C1 C10) and 14 subtypes

69 Mechanisms of neuron-type functions?

70 Fibroblast growth factor 13 (FGF13) is highly expressed in MHNs (C1, C2, C4, C5 and C6) Yang et al. (2017) Neuron

71 FGF13 is selectively required for sensing the noxious heat stimulation

72 Noxious heat-induced fmri signal is reduced in the brain of FGF13-deficient mouse

73 FGF13 is required for noxious heat-induced firing of action potentials

74 TRPV1 channel is expressed in C1 and C2, and contributes to heat (> 50 o C) nociception WT Trpv1 -/- Caterina et al. (2000) Science

75 FGF13 is required for noxious heat-induced firing of action potentials

76 Na V channels in DRG neurons Na V 1.7 mutations in human Loss of function Gain of function

77 FGF13 directly interacts with Na V 1.7

78 FGF13 maintains the Na V 1.7 level in plasma membrane during noxious heat stimulation

79 Heat increases the FGF13/Na V 1.7 interaction

80 Model for the mechanism of noxious heat sensation

81 Summary 1. We identify 10 types and 14 subtypes of mouse DRG neurons, including 6 types of mechanoheat nociceptors (MHNs). 2. FGF13 in MHNs selectively regulates the heat nociception by interacting with Na V 1.7. Transcriptome data sources: 1. GEO: GSE ibrain Project:

82 Two ascending pathways of somatic sensation

83

84 Somatotopic organization of dorsal column nuclei

85 Neuronal pathway tracing

86

87 Dorsal column-medial lemniscal pathway

88 Spinothalamic pathway

89 Signaling processes in the cortex The location and amount of cortical area dedicate to a particular function The area of cortex and the mass of the body part: not proportional! Hands, lips have larger representation Neurons are organized into a neural map of the body.