Development and anatomical organization of the nervous system I Contents:

1. Functional organization of the nervous system 2. Development of nervous systems 2.1 Cnidarians: polyps and medusae (Hydra) 2.2 Flatworms and roundworms (C. elegans) 2.3 Molluscs (Aplysia and Octopus) 2.4 Arthropodes (Drosophila) 3. Pattern formation in Drosophila

Literature: Kandel ER, Schwartz JH, Jessell TM. Principles of neural science. New York: McGraw-Hill *** Kahle, W. Taschenatlas der Anatomie. Band 3: Nervensystem und Sinnesorgane. Stuttgart: Thieme *** Functional organization of the nervous system

Information processing (integration)

Sensory Input (receptors)

Motor Output (muscles)

Somatic part of the PNS (Campbell et al., Biologie) Development of nervous systems

Cnidarians („Nesseltiere“): polyps and medusae - „Lowest“ organism with a neuronal network

Polyps: Sessile form of the Cnidarian building plan Hydra Medusae (yellyfish): free-floating form of the Cnidarian building plan Aurelia aurita

Aurelia aurita („Ohrenqualle“) Hydra Development of nervous systems

Nervous system of Cnidarians

Distributed nerve net (no central nervous system) as the sole nervous system (similar to the autonomous nerve system at higher organisms)

Sensory Motor Integration Input Output (Interneurons) (receptors) (muscles) • mechanical, chemical and electrical signals • changes in light and temperature Development of nervous systems

Nervous system of Cnidarians

Hydra - Most simple nervous system: Hydra → Model system - Reaction to mechanical, chemical (e.g. glutathione) and electrical stimuli as well as changes in light and temperature

- Peptide neurotransmitters (no low molecular weight transmitters) >12 neuropeptides with transmitter function Hydra - No glial cells, no myelinization

- Symmetrical synapses (no distinction between axons and dendrites) Development of nervous systems

Nervous system of Cnidarians

Medusae

- Begin of a functional differentiation Aurelia aurita („Ohrenqualle“) net of multipolar nerve cells below the epithelial cell layer in connection to sensory cells („exumbrellar nerve ring“): sensory function

net of nerve cells on top of muscle cells („subumbrellar nerve ring“) with electrical coupling: motor coordination Development of nervous systems Nervous system of flatworms and roundworms

„Lowest“ organisms with a central nervous system - Contain a body axis - Contain a spezialized head region („cephalization“) - Contain an accumulation of nerve cells in the head region (nerve ring, „brain“) Important model organism: Caenorhabditis elegans (roundworm, nematode) Development of nervous systems Nervous system of flatworms and roundworms

Formation of a medullary strand (“Markstrang”) in the ventral cord: - forms transition between diffuse and centralized nervous system: nerve cells arrange themselves into strand-like associations, but the cell bodies are not yet exclusively limited to ganglia Development of nervous systems Nervous system of flatworms and roundworms C. elegans as model organism to study the development of the nervous system - Complete sequence information (1998) - 302 nerve cells with defined origin (about 1000 cells in total) - Complete electron microscopic reconstruction of the nervous system (Brenner and co-workers)

Sydney Brenner † 5.4.2019 Nobel prize, 2002 Development of nervous systems Nervous system of molluscs

High complexity: Spectrum from relatively simple central nervous systems (similar to C. elegans) to the most developed nervous systems of the evertebrates (cephalopods, e.g. octopus)

Model organism with a relatively simple central nervous system: Marine snail Aplysia californica with about 20,000 CNS neurons Development of nervous systems Nervous system of molluscs

Aplysia: Nervous system is organized in separate ganglia

Model organism for analysis of cellular mechanisms of simple forms of implicit learning (gill retraction reflex): - Habituation - Sensitization - classic conditioning Development of nervous systems Nervous system of molluscs

Aplysia: Model organism for analysis of cellular mechanisms of simple forms of implicit learning

Classic conditioning: conditioned stimulus: tactile stimulus of the siphon unconditioned stimulus: electrical shock at the tail Development of nervous systems Nervous system of molluscs

Aplysia: Model organism for analysis of cellular mechanisms of simple forms of implicit learning

Classic conditioning: conditioned stimulus: tactile stimulus of the siphon unconditioned stimulus: electrical shock at the tail Development of nervous systems Nervous system of molluscs

Aplysia: Model organism for analysis of cellular mechanisms of simple forms of implicit learning

Operant conditioning (an originally insignificant spontaneous behavior can be preferred / avoided by reinforcement or punishment) in Aplysia

Hawkins, R.D., Clark, G.A., Kandel, E.R. (2006) Operant conditioning of gill withdrawal in Aplysia“, J. Neurosci. 26:2443-2448

Aplysia was taught to keep his gills contracted to avoid electrical shock Development of nervous systems Nervous system of molluscs Octopus: - Highly developed nervous system (around 42 million nerve cells in the brain) - Good learning ability - Complex behavior is highly visually controlled - Peripheral and central nervous ganglia - Central nervous ganglia are called lobes (> 30), which together form the brain and are enclosed by a cartilage capsule

Chemotactile and visual centers are largely separated and each consist of four lobes (topical organization) Development of nervous systems Nervous system of arthropodes Subdivision of the arthropods in - Chelicerata (spider-like) - Crustacea (crayfish) - Tracheata (millipedes and insects)

Insects (Insecta) are the experimentally most important and species-rich group

CNS consists of dorsal brain (fused cerebral ganglia) and ventral nerve cord Development of nervous systems Nervous system of arthropodes

Brain: Complex fine structure consisting of cell body regions (nuclei), fiber bundle areas (nerve tracts), multiple neuropil centers (network of nerve fibers and glial cell processes)

Brain is divided into three parts: protocerebrum, deutocerebrum, and tritocerebrum with functional spezialization Development of nervous systems Nervous system of arthropodes

Protocerebrum: two hemispheres that merge laterally into the optical lobes, contains central body (probably motor control) and paired mushroom bodies (multimodal integration center for coordination of olfactory and visual excitation) Development of nervous systems Nervous system of arthropodes

Deutocerebrum: origin of the antenna nerves with a sensory and motor component

olfactory and mechanosensory receptor neurons end in different areas of the Deutocerebrum: → Topical organization

Tritocerebrum: innervation of the head surface, origin of the frontal connective Development of nervous systems Nervous system of arthropodes

ventral nerve cord: - functional equivalent of the vertebrate spinal cord - consists of paired segmental ganglia running along the ventral midline of the thorax and abdomen like a “rope ladder” (“Strickleiter”) - contains efferent projecting motor neurons and afferent sensory fibers Development of nervous systems Nervous system of arthropodes

Formation of the ganglion chain is a model system for axonal pathfinding: Pioneer neurons create the fiber tracts of the commissures (cross-connections) and connectives (longitudinal connections) Pattern formation in Drosophila

Pattern formation: Regionalization of the nervous system Mechanisms of pattern formation: 1. Segmentation: Subdivision of the neural tube into axially repeated, module-like units (neuromeres) Basis: differential gene activity (segmentation genes) 2. Determination of the anatomical identity of the individual segments: Discovery of the so-called “homeotic genes” in Drosophila (in homologous form also in vertebrates) as regulatory genes

Mutations in the homeotic genes lead to pattern formation anomalies Pattern formation in Drosophila

Homeotic genes in vertebrates In vertebrates, homeotic “HOX genes” have a spatial expression pattern comparable to that in Drosophila

Humans have 39 HOX genes, which are organized in 4 clusters and play an important role in the development of the CNS, skeleton, limbs and various internal organs

Some limb malformations are due to mutations in the HOX genes (Goodman (2002) Limb malformations and the human HOX genes. Am. J. Med. Genet. 112:256-265)