Sensitive and critical periods during neurotypical and aberrant neurodevelopment: a framework for neurodevelopmental disorders.

During sensitive and critical periods, the brain undergoes significant plasticity from the level of individual synapses and neuronal networks up to the level of behaviour. Both sensitive and critical periods during neurotypical development of the young animal provide a framework to the early temporally-regulated modifications that occur in the nervous system. In neurodevelopmental disorders (NDD), notably autistic syndromes and intellectual disability, children exhibit developmental delays in motor, social and sensory processes and often miss key developmental milestones. In corresponding genetic NDD mouse models, recent data reveal temporally-regulated and in some cases, transient impairments in many neuronal and behavioural phenotypes during development. However, the mechanisms underlying these impairments in NDDs and their potential links with neurobiological mechanisms governing neurotypical development are not fully investigated. This article highlights the potential for the use of known critical and sensitive periods during vertebrate development to investigate and advance our understanding of the neural bases underlying impairments in these developmental disorders of the nervous system.

Amino acid neurotransmitter release and learning: a study of visual imprinting.

The intermediate and medial part of the hyperstriatum ventrale (IMHV) is an area of the domestic chick forebrain that stores information acquired through the learning process of imprinting. The effects of visual imprinting on the release of the amino acids aspartate, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glycine and taurine from the left and right IMHVs in vitro were measured at 3.5, 10 and 24 h after training. Chicks were exposed to an imprinting stimulus for 1 h, their preferences measured 10 min afterward and a preference score calculated as a measure of the strength of learning. Potassium stimulation was used to evoke amino acid release from the IMHVs of trained and untrained chicks in the presence and absence of extracellular Ca2+. Ca2+-dependent, K+-evoked release of glutamate was significantly (34.4%) higher in trained than in untrained chicks. This effect was not influenced by time after training or by side (left or right IMHV). Training influenced the evoked release of GABA and taurine from the left IMHV at both 3.5 and 10 h. The training effects at the two times were statistically homogeneous so data (< or = 10 h group) were combined for each amino acid respectively. For this < or = 10 h group, evoked release increased significantly with preference score. In contrast, for the 24 h group, evoked release of GABA and taurine was not significantly correlated with preference score. There were no significant correlations between preference score and GABA or taurine release in the right IMHV at any time, nor in the absence of extracellular calcium. No significant effects of training condition, time or side were observed for any other amino acid in the study. The present findings suggest that soon after chicks have been exposed to an imprinting stimulus glutamatergic excitatory transmission in IMHV is enhanced, and remains enhanced for at least 24 h. In contrast, the learning-related elevations in taurine and GABA release are not sustained over this period. The change in GABA release may reflect a transient increase in inhibitory transmission in the left IMHV.

Rapid report: postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus.

1. The biologically relevant rules of synaptic potentiation were investigated in hippocampal slices from adult rat by mimicking neuronal activity seen during learning behaviours. Synaptic efficacy was monitored in two separate afferent pathways among the Schaffer collaterals during intracellular recording of CA1 pyramidal neurones. The effects of pairing presynaptic single spikes or bursts with postsynaptic single spikes or bursts, repeated at 5 Hz ('theta' frequency), were compared. 2. The pairing of ten single evoked excitatory synaptic events with ten postsynaptic single action potentials at 5 Hz, repeated twelve times, failed to induce synaptic enhancement (EPSP amplitude 95% of baseline amplitude 20 min after pairing; n = 5). In contrast, pairing the same number of action potentials, but clustered in bursts, induced robust synaptic potentiation (EPSP amplitude 163%; P < 0.01, Student's t test; n = 5). This potentiation was input specific, long lasting ( > 1 h; n = 3) and its induction was blocked by an antagonist at NMDA receptors (20-50 microM D(-)-2-amino-5-phosphonopentanoic acid; EPSP amplitude 109%; n = 6). 3. Presynaptic bursting paired with postsynaptic single action potentials did not induce input specific synaptic change (113 % in the test input vs. 111 % in the control; n = 8). In contrast, postsynaptic bursting when paired with presynaptic single action potentials was sufficient to induce synaptic potentiation when the presynaptic activity preceded the postsynaptic activity by 10 ms (150 vs. 84 % in the control input; P < 0.01; n = 10). 4. These results indicate that, under our conditions, postsynaptic bursting activity is necessary for associative synaptic potentiation at CA1 excitatory synapses in adult hippocampus. The existence of a distinct postsynaptic signal for induction of synaptic change calls for refinement of the common interpretation of Hebb's rule, and is likely to have important implications for our understanding of cortical network operation.

Field splinting of suspected fractures: preparation, assessment, and application.

Serious sports-related extremity injuries require a careful initial evaluation and subsequent protection of the extremity. After ruling out life-threatening injury and assessing neurovascular status, the examiner must decide whether a splint is required. The on-site physician needs to know which of a wide variety of preformed splints and splinting materials are best for the most common upper- and lower-extremity injuries. Appropriate padding, fit, and materials ensure optimal protection.