Overproduction Of Synapses Research Articles

Limited synapse overproduction can speed development but sometimes with long-term energy and discrimination penalties.

Neural circuit development requires that synapses be formed between appropriate neurons. In addition, for a hierarchical network, successful development involves a sequencing of developmental events. It has been suggested that one mechanism that helps speed up development of proper connections is an early overproduction of synapses. Using a computational model of synapse development, such as adaptive synaptogenesis, it is possible to study such overproduction and its role in speeding up development; it is also possible to study other outcomes of synapse overproduction that are seemingly new to the literature. With a fixed number of neurons, adaptive synaptogenesis can control the speed of synaptic development in two ways: by altering the rate constants of the adaptive processes or by altering the initial number of rapidly but non-selectively accrued synapses. Using either mechanism, the simulations reveal that synapse overproduction appears as an unavoidable concomitant of rapid adaptive synaptogenesis. However, the shortest development times, which always produces the greatest amount of synapse overproduction, reduce adult performance by three measures: energy use, discrimination error rates, and proportional neuron allocation. Thus, the results here lead to the hypothesis that the observed speed of neural network development represents a particular inter-generational compromise: quick development benefits parental fecundity while slow development benefits offspring fecundity.

Plasticity in the developing brain: Implications for rehabilitation

Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive and responsible for neurological disorders in some situations. Basic mechanisms that are involved in plasticity include neurogenesis, programmed cell death, and activity-dependent synaptic plasticity. Repetitive stimulation of synapses can cause long-term potentiation or long-term depression of neurotransmission. These changes are associated with physical changes in dendritic spines and neuronal circuits. Overproduction of synapses during postnatal development in children contributes to enhanced plasticity by providing an excess of synapses that are pruned during early adolescence. Clinical examples of adaptive neuronal plasticity include reorganization of cortical maps of the fingers in response to practice playing a stringed instrument and constraint-induced movement therapy to improve hemiparesis caused by stroke or cerebral palsy. These forms of plasticity are associated with structural and functional changes in the brain that can be detected with magnetic resonance imaging, positron emission tomography, or transcranial magnetic stimulation (TMS). TMS and other forms of brain stimulation are also being used experimentally to enhance brain plasticity and recovery of function. Plasticity is also influenced by genetic factors such as mutations in brain-derived neuronal growth factor. Understanding brain plasticity provides a basis for developing better therapies to improve outcome from acquired brain injuries.

A converging-methods approach to fragile X syndrome.

Converging approaches across domains of brain anatomy, cell biology, and behavior indicate that Fragile X syndrome, arising from impaired expression of a single gene and protein, appears to involve an aberration of normal developmental processes. Synapse overproduction and selective elimination, or pruning, characterize normal brain development. In autopsy tissue from Fragile X patients and in a knockout mouse model of the disease, synapse overproduction appears to occur unaccompanied by synapse pruning and maturation, leaving an excess of immature spine synapses in place. The absence of the Fragile X protein seems to impair the synthesis of important proteins at synapses. The developmental outcome in Fragile X is a nervous system that is relatively disorganized, resulting in disrupted perceptual, and cognitive social, behavior.

Development of full-length Trk B-immunoreactive structures in the prefrontal and visual cortices of the macaque monkey.

Distribution and morphological changes of cells containing the signal transducing neurotrophin receptor, full-length Trk B (fl-Trk B), were investigated in the prefrontal cortex (area FD) and the primary visual cortex (area OC) of the macaque monkey between embryonic day 140 and the adult stage. In area FD at the adult stage, fl-Trk B immunoreactivity was mainly observed in the pyramidal cells in layers II/III, V and VI. Small numbers of granule cells in layer IV were immunopositive. Bipolar and multipolar cells in layer II were rarely immunoreactive. At embryonic day 140, the number of fl-Trk B immunoreactive pyramidal cell was high, and gradually decreased until the adult stage. In layer IV, the number of fl-Trk B-ir cells was also high at embryonic day 140, and decreased remarkably from postnatal day 7 to the adult stage. On the other hand, in area OC at the adult stage, cells in layers II/III, IV, V and VI were fl-Trk B immunopositive. From embryonic day 140 until adulthood, the cells in layer IVc were fl-Trk B immunoreactive. The strongest fl-Trk B immunoreactivity in areas FD and OC occurred at postnatal month 6, coinciding with the time of the synapse overproduction. These findings suggest that ligands of fl-Trk B, such as BDNF and NT4/5 may be involved in the development and maintenance of the monkey cerebral cortices.

Positron emission tomography in mitochondrial diseases.

1. Ontogeny of glucose utilization rates in brain Studies of cerebral glucose metabolism with positron emission tomography (PET) and 2-deoxy2-[ 18 F]fluoro-D-glucose (FDG) in infants and children can provide important information on human brain functional development relevant to the study of mitochondrial disorders. The pattern of glucose metabolism in the human neonatal brain is markedly different from that of adults; typically, four brain regions are metabolically prominent: sensorimotor cortex, thalamus, brainstem and cerebellar vermis [1,2]. Phylogenetically, these are relatively old structures which dominate the behavior and mediate primitive intrinsic reflexes of newborns. During the first year, the ontogeny of cerebral glucose metabolism proceeds in phylogenetic order, correlating well with behavioral maturation of the infant. By 1 year, cerebral glucose metabolic patterns qualitatively resemble that of normal young adults [2,3]. Quantitative analysis of local cerebral metabolic rates for glucose (LCMRglc) shows that the brain follows a protracted glucose metabolic maturational course. Neonatal LCMRglc values, which are about 30% lower than adult rates, rapidly increase to exceed adult values by 2‐3 years in the cerebral cortex and remain at these high levels until about 8‐10 years, when LCMRglc decline to reach adult rates by 16‐18 years [2,3]. Correlation of these cerebral glucose metabolic trends with other neurodevelopmental events suggests that the ascending portion of rapid LCMRglc increase corresponds to the period of rapid overproduction of synapses and nerve terminals known to occur in the human brain. The ‘plateau’ period during which LCMRglc exceeds adult values corresponds to the period of increased cerebral energy demand as a result of transient exuberant connectivity. That segment of the metabolic maturational curve describing the LCMRglc decline corresponds to the period of selective elimination or ‘pruning’ of excessive connectivity, and marks the time when developmental plasticity markedly dimishes in humans [3]. This interpretation is supported by studies in animal models. For example, the kitten brain also goes through a protracted period of metabolic maturation, including a phase when LCMRglc exceeds values for the adult cat [4]. Furthermore, the ascending portion of the LCMRglc maturational curve for the kitten visual cortex, seen between 3 weeks and 3 months, corresponds to the ‘critical period’ and period of rapid synaptogenesis for this structure in the cat. Similarly, there is a correspondence

Synaptogenesis in the primary visual cortex of the tree shrew (Tupaia belangeri)

The primary visual cortex of the tree shrew is characterized by the lack of ocular dominance columns. The two eyes are represented in sublayers of laminae 3 and 4. In an earlier study using the transneuronal transport we observed that the geniculate afferents from the two eyes do not initially overlap and then segregate into their appropriate sublaminae. The final distribution pattern can already be observed during the early postnatal period. Since segregation and elimination of afferent terminal branches do not seem to take place, we wanted to investigate whether or not an overproduction of synapses can be observed as in several other animals. We examined layers 3B, 3C, 4A, and 4B, which receive afferents from the retina via the lateral geniculate nucleus, from P5 to maturity by using the electron microscope. The brain tissue was excised in the region where the central vision is represented in adult animals. Then we determined the density of synapses per 100 microns 2 neuropil for each of the four sublayers at the ages P5, P15, P19, P23, P31, and P42 and in the adult animal (AD). In determining the neuropil we measured the size of two additional compartments, i.e., the compartments consisting of perikarya and of blood vessels. At a higher resolution we determined the fraction of Gray type I and type II synapses in each sublamina and in each developmental stage. The size of the neuropil increases from 57% at P5 to 81% in AD whereas the compartment of perikarya decreases from 42% to 15% and the compartment of blood vessels increases from 1.3% to 3.9%. The synaptic density starts with very low values (3.5/100 microns 2) at P5. Then it increases rapidly and attains a maximal rate of increase during the period of eyelid opening. After this period the increase is slowed down and approaches the adult value (12.5/100 microns 2) slowly. An overproduction of synapses could not be observed. The percentage of type I and type II synapses also changes during this period. The fraction of type I synapses amounts to 73% at P5 and increases to 92% in AD. The increase in density of type I synapses is continuous and does not show any sign of overproduction. The density of type II synapses rapidly reaches it final value and then remains constant. Possibly there is a slight overproduction during the period of eyelid opening.(ABSTRACT TRUNCATED AT 400 WORDS)