Discuss the roles of development learning Essay

The nervous system is responsible for the initiation, propagation and co-ordination of animal behaviour. How it is constructed and what factors are involved encompasses many fields of biology, from ethology and neurophysics to evolution. In this essay I will describe the roles of development learning and evolution in the construction of the nervous system and give experimental evidence that backs up these theories. Evolution Evolution deals with the origins of the nervous system, where it comes from determines how it will be constructed. This will have direct consequences on the relative fitness of an individual as the layout of the nervous system relates to how the animal behaves. Phylogeny is very important therefore to analyse how changes in the nervous system relate to the evolution of behaviour. The only realistic way of studying the evolution of nervous systems, particularly the events, which lead to, their current day form, is through comparative biology. By comparing closely related species in similar niches, the difference in their behaviour must have a genetic/nervous system origin. A good example of how behaviour can be genetic in origin and show that nervous systems can evolve to create different behavioural responses is found in deer. The white tailed deer odocoileus virginianus and the mule deer O. hemionus use different gaits when alarmed. The white deer gallop and the mule deer stott. This alone doesn’t confer that the difference is due to their nervous systems but the genetic origin for the behaviour is inferred when a cross between the two species results in a hybrid that bounds when alarmed. In order to attain quantitative data the use of complex nervous systems, such as mammals, is unfeasible. A simpler nervous system is better suited and comparisons can then be extrapolated for the more complex animals. Within the invertebrates the model organism is, as ever, Drosophila. Since its genome has been sequenced and the relatively short generation time it plays a key role in the study of all type of nervous system construction. Zebra fish have been termed â€Å"flies with backbones† and are perfect for the study of nervous system development in vertebrates. However these relatively simple organisms are still too complex to study fully and so scientists tend to use a part of a nervous system for detailed analysis. The Crustacean Stomatogastric Ganglion STG, which comprises of only 30 ganglions, is most popular for several reasons, mainly because it has been preserved for about 350 million years and is seen across many taxa. This allows for comparison on a smaller scale and although the overall synaptic circuitry is similar there are differences in the relative strength of connections and the amount of electrical coupling across the taxa. The reason why the STG is seen across so many taxa is because on the whole the nervous system is a very evolutionary conserved organ. This reflects its importance to an animal. As it is so conserved certain inferences can be made regarding the evolution of the nervous system. The first is that the neural networks must be pretty similar across species meaning that the nervous system is more of a generalist than a specialist. Therefore only small changes to the nervous system are needed in order to produce markedly different behaviours. It is these behaviours that are then subsequently acted upon by natural selection and contribute to the nervous system layout in the next generation. Development Once the genetic instructions that determine the constitution of the nervous system have been selected the next step in the construction of the nervous system is the subsequent application of that code, the development. The nervous system develops during embryogenesis and continues in some form or another throughout the animals’ life, but that latter stages of this development I shall relate to the learning part of this essay. From before we have learnt that the basic mechanisms for constructing a nervous system are highly conserved during evolution. There is a set of general tools that are used by all species and perhaps only a few specialist tools are needed in order to make an individual nervous system. The nervous systems building blokes are neurones, and since all cells derive from the fusion of the male and female gametes there must be factors telling cells to become neurones. The process of creating neurones is called neurogenesis and the mechanism is neural induction, the committal of cells to a neural fate. It appears that this process is a permissive one, one where the local inactivation of inhibitors in the ectoderm, creates neurones. The factors that drive neural induction are basic helix loop helix type proteins and homologues have been found in both vertebrates and invertebrates, thus stressing their importance. Also the helix loop helix is a very evolutionary old mechanism for gene regulation and the fact that neural cells can be coerced The next step is the creation of asymmetry in the ectoderm. This allows a more complex, coordinated nervous system to develop. The formation of layers, maps and modules is an essential feature of neural development in â€Å"higher† animals. The process of creating asymmetry, and so the nervous system as a whole, can be divided into three parts. 1. Pathway Selection The growing tips of the neurones travel great distances in order to reach their target. When confronted with a series of choice points they manage to travel in the right direction. 2. Target Selection Once the neurone has arrived in the correct neighbourhood the contact and recognise their correct target, usually a localised set of neurones. 3. Address Selection Refinement occurs as axonal terminals retract and expand to select a specific subset of cells from within the overall target. Capable of transforming a coarse, grained and overlapping projection into a refined and highly tuned pattern of connections. The mechanisms of these processes are still being elucidated although some basic principles have begun to crystallise. The development of connectivity most probably involves general â€Å"algorithmic† principles. The experiments performed in the last ten years have proved to provide strong evidence for many of the previous hypothesis. Pathway and Target Selection Mechanisms Axonal growth needs to be controlled in order for a functioning nervous system to develop, however this does not necessarily mean that the neurons have to be firing in order to be set up. The pathway and target selection mechanisms are believed to be autonomous, activity independent. This has been demonstrated by work done on Ambystomid Urodeles (Twitty and Johnson 1934). The embryos were paralysed with TTX for a period of days until the larvae would normally move and feed for themselves. At that point the TTX induced paralysis wore off and surprisingly the animals soon began to swim and eat in a remarkably normal fashion. In the 1970’s a theory developed that the innervation of muscles is largely at random, with patterns emerging later by the elimination of connections and cell death. This appears to be a very costly mechanism as neurones are being created only to soon be destroyed. This theory was abandoned when studies were performed on chicks (Landmesser 1978, 1980) and zebra fish (Eisen et al, 1986) that showed specific motor neurones innervate their target muscle with relatively few error from the outset. They possess unique identities that allow them to differentially respond to the choice point region, follow particular pathways and innervate specific muscle. Sperry first postulated the mechanism for the directionality of growth cone movement in 1963 when he suggested the chemoaffinity hypothesis. Neuronal growth cones were specifically guided toward their correct targets by specific chemotactic cues and proposed gradients of chemical labels. The neurones enhance and transduce the signals from the extracellular matrix to remodel cytoskeletal elements. This form of gradient-mediated chemotaxis is essential in the formation of more complex structures such as layers and maps. However the directional sensing of neurones in a 2D field such as the tectum is strong evidence for guidance by gradients despite any molecular evidence. Theoretical analysis show that requirements for map formation are simple for target tissue; there must be at least one gradient for each of the tangential dimensions. For co-ordinated simultaneous development of the nervous system there must be a series of different gradients to ensure that neurones do not switch tracks or get confused when the tissue becomes saturated with the same molecule. This has been seen when the preferred neurone’s pathway has been ablated and they have chosen not to move down other axons. There is also compelling evidence for chemorepressor molecules which serve to deter axonal growth. Studies by Kampfhammer and Raper in the past 15 years have shown the mutual avoidance of the CNS axons and the PNS axons. Evidence is also accumulating that the developing midline of the CNS of both vertebrates and invertebrates provides both attractive and repulsive guidance cues. Many CAMs, integrins and extracellular matrix molecules have been implicated in growth cone guidance, owing to their expression in vivo. The experimental evidence for these molecules being directly responsible through the use of immunoassays and mutation is scare. One series of molecules has been identified though, small GTP proteins of the rho family that regulate the focal adhesion, membrane ruffling and filopodial protrusion of neurones. However assessing the accuracy of targeting is difficult. The mapping efficiency, although higher than simple dorsal-ventral distinctions is still far below the accuracy of some sections in the nervous system, namely vision. Other theories have had to be formulated in order to explain the increase in resolution. Selective cell death has been postulated but the one with the most evidence is activity dependent self-organisation. Address Targeting Activity dependent plasticity seems uniquely suited to refine local axonal projections beyond the accuracy achieved by genetic instruction alone. Schmidt and Edwards (1983) demonstrated the effects of activity dependent on creating a fine-grained map in the visual cortex of a fish. The fishes’ eye was crushed, if left to heal it eventually regenerated and regained the retinotectal map. If the regeneration was interrupted by the addition of TTX the fine-grained map failed to form although the coarse topographic map still formed. This suggests the relationship between refinement and neuronal activity. Further studies revealed that retinal ganglion cells fired synchronously, both during embryogenesis (intrinsic origin) and after (extrinsic origin), suggesting that it was not the neural activity per se but the temporal and spatial firing that refines axonal connections. So called â€Å"cells that fire together wire together†. But the converse is also true, that for any kind of axonal remodelling not only must appropriate connections be strengthened but inappropriate ones must be weakened. The evidence for the synchronous firing of neurones continuing into later life means that the environment is constantly altering the neural networks. Learning As we have learnt the constantly changing neural networks are directly related to the extrinsic information they receive. The definition of learning is the acquisition of new information and memory is the retention of that information over time. It is clear now how the two are related in terms of the nervous system, the process of learning effects the construction of the nervous system by the storage of the information gained. The acquisition of information may come in different forms, associative between two stimuli or non-associative such as habitualisation. However they do not directly alter the nervous system, the nervous system is altered by the way in which it decides to store this data. The first insight was made by Ebbinghaus (1913) where he determined different phases of memory storage. It was Milner who first made the distinction between short term and long-term memory, the two different types of data storage, which are separated on a temporal basis. Short-term storage involves functional changes in the strength of pre-existing synaptic connections. This was demonstrated by experiments on Alpysia. Conditioning was performed and it was reflected in the neural circuitry as a greatly enhanced strengthening of the input connections of the sensory neurones to their target cells. Murphy and Glanzman (1997) provide compelling evidence for the changes in synapse being causally involved in the learning of new information through their work on the receptors of glutamate in the synapses. Long-term memory storage involves the synthesis of new protein and the growth of new connections (Flexner et al 19650. Given this information how is short-term memory converted into long-term memory? The answer is not yet fully understood, but experiments have given some clues as t how it occurs. Serotonin is thought to be important (Kandel 1976) as it increases the intracellular concentration of the secondary messenger cAMP. Martin et al (1997) suggests that new genes are being activated in the nucleus have their products distributed widely, but that the products only persistently strengthen those synapses that have somehow been marked by short term facilitation. It also appears that the protein CREB is required for functional plasticity but it is not sufficient for morphological plasticity. The changes to the gross structure of the nervous system in response to learning can be seen in an experiment performed on monkeys that were trained to preferentially use only some fingers. The cortical representation of those fingers expanded (Merzenich and colleagues). This has also been demonstrated with violinists who show a disproportionate representation of their left hand (fingering hand) when compared to their right hand (bow movement). Conclusions The roles played by each factor described here each have their own specific effect on the construction of the nervous system. The evolutionary aspect controls the â€Å"blueprints† of the nervous systems that are hard coded into the DNA of the animal. However it is not specifically the genetic makeup of the nervous system that natural selection acts against, rather the phenotype of the nervous system, which is the combination of the developmental and the learning factors. The evolutionary factors alter the genotype, the only source of variation that can be passed down to their offspring. The development can only attempt to recreate the layout as specified by the different alleles; it cannot exceed them in terms of functionality. The true source of variation depends on the extrinsic information obtained and stored in memory, but that us not able to cross generations (with the exception of tradition) and so could be an explanation for the high evolutionary conservation of the nervous system. Bibliography Gierer, A & Muller, C. M 1995 development of layers maps and modules. Current Opinion o Neurobiology 5 91-97 Goodman, C. S & Shatz, C.J. 1993 Developmental mechanisms that generate precise patterns of neuronal connectivity Neuron 10 (Suppl. ). 77-98 Lumsden, A. & Jan, Y-N. 1997 Development. Editorial overview: the end of the beginning? Current Opinion in Neurobiology 7 3-6 Kandel, E. R. & Pittenger, C. 1999 The past, the future and the biology of memory storage Philosophical transactions of the Royal Society London B 354 2027-2052 Katz, P. S & Harris-Warwick R. M. 1999 The evolution of neuronal circuits underlying species-specific behaviour Current Opinion in Neurobiology 9 628-633.