Which of the following instances best exemplifies the use of primary research?

Abstract

Dendrites are exquisitely specialized cellular compartments that critically influence how neurons collect and process information. Retinal ganglion cell (RGC) dendrites receive synaptic inputs from bipolar and amacrine cells, thus allowing cell-to-cell communication and flow of visual information. In glaucoma, damage to RGC axons results in progressive neurodegeneration and vision loss. Recent data indicate that axonal injury triggers rapid structural alterations in RGC dendritic arbors, prior to manifest axonal loss, which lead to synaptic rearrangements and functional deficits. Here, we provide an update on recent work addressing the role of RGC dendritic degeneration in models of acute and chronic optic nerve damage as well as novel mechanisms that regulate RGC dendrite stability. A better understanding of how defects in RGC dendrites contribute to neurodegeneration in glaucoma might provide new insights into disease onset and progression, while informing the development of novel therapies to prevent vision loss.

Dendrites

The dendrites of supraoptic nucleus oxytocin neurons are broad and bundled together in the ventral glial lamina of the nucleus. Dendrites of magnocellular paraventricular nucleus oxytocin neurons project toward the third ventricle. There are many synaptic boutons on these dendrites. However, the dendrites of oxytocin neurons not only receive signals but also transmit them (Figures 3 and 4). Oxytocin released from the dendrites of magnocellular neurons is an essential component of the mechanism that causes synchronized burst-firing of the neurons during parturition and suckling in lactation, and dendritic oxytocin release is a mechanism of more widespread volume transmission in the brain. Dendritic release of oxytocin can occur independently of initiation of spikes in the cell body, and it is the result of activation of mechanisms that increase intracellular Ca2+; both oxytocin and α-melanocyte-stimulating hormone (from the arcuate nucleus projection) act in this way.

Events at Dendrites

Dendrites (dendron=tree) are membranous tree-like projections arising from the body of the neuron, about 5–7 per neuron on average, and about 2 μm in length. They usually branch extensively, forming a dense canopy-like arborization called a dendritic tree around the neuron. The size of the dendritic tree is enormous compared to the soma – the size of the body of a neuron has been compared to a tennis ball placed in a large room and the size of dendritic tree to the large room itself, and consequently the dendritic membrane covers a much greater surface area than that of the soma. As shown above in ‘Axodendritic synapses’, axons preferentially terminate on the dendrites. And it is not surprising that about 75% of the dendritic membrane of a typical neuron is said to participate in synaptic transmission!

Dendritic Spines

Dendrites show the presence of numerous spiky membranous protrusions called dendritic spines that deserve special mention because these are the structures that actually synapse with the axon’s terminal bulbs (Fig. 6.2). A single dendrite has tens of thousands of dendritic spines (on average, 200 000 dendritic spines per neuron!). Usually they have narrow stalks with bulb-like heads.

Figure 6.2. The dendritic spines.

Dendritic spines are highly dynamic structures – changing their forms and synaptic connections with the passage of every signal to them. They may appear or disappear constantly with each given stimulus, giving the neuron its characteristic dendritic plasticity, which was shown to be a part of synaptic plasticity (see below).

Synaptic plasticity is defined as the ability of neurons to bring about changes in the connections between neuronal networks in response to use or disuse. Synaptic plasticity is of two types: 1) mediated by the NTs, and 2) mediated by dendritic plasticity, both discussed in detail in Chapter 3. We are here concerned with the capacity of the dendritic tree to form new synapses or break old synapses in accordance with the stimuli that reach it from the axon terminals (Figs 6.3 & 3.9). The dendritic spines are capable of changing their forms rapidly in a matter of minutes or hours (Barrett et al. 2012, p. 125), which confers a great deal of dendritic plasticity to the neurons. This versatile property of quick response is especially true of neurons in the cortex, and is essential for rapid acquisition of memory and to enable learning. The reader may refer to Chapter 3, p. 70 to learn of other remarkable features of dendritic spines.

Figure 6.3. Dendritic plasticity.

Dendrites

The dendrites of supraoptic nucleus oxytocin neurons are broad and bundled together in the ventral glial lamina of the nucleus. Dendrites of magnocellular paraventricular nucleus oxytocin neurons project toward the third ventricle. There are many synaptic boutons on the dendrites. However, the dendrites of oxytocin neurons not only receive signals, they also transmit (Figs. 3 and 4). Oxytocin released from the dendrites of magnocellular neurons is an essential component of the mechanism that, via local positive feedback through oxytocin receptors, causes synchronised burst-firing of the neurons during parturition and suckling in lactation, and dendritic oxytocin release is a potential mechanism of more widespread volume transmission in the brain. Dendritic release of oxytocin can occur independently of initiation of spikes in the cell body, and is then the result of activation of mechanisms that increase intracellular Ca2+; both oxytocin and α-melanocyte stimulating hormone (α-MSH, from the arcuate nucleus projection) act in this way.

SNr and GPi

The SNr and the GPi (or EP in rodents) represent the major output nuclei of the basal ganglia, sending their axons to the thalamus and thence back to the cortex or to subcortical structures involved in the control of behavior, including the superior colliculus, parvicellular reticular formation, lateral habenula, and the PPN (Figure 1). The relative importance of the two output nuclei in the control of behavior varies among species of different orders. Thus, output to thalamus from the GPi in primates is probably more important than the output from the SNr whereas in rodents, the output from the SNr is probably more important than that from the EP.

Basal ganglia output neurons are large GABAergic neurons with long, infrequently branching, aspiny dendrites. In the GPi at least, they are similar to GPe neurons in that their dendrites are arranged in such a way as to expose their maximum surface to the incoming striatal afferents. Their major input is from the MSNs of the striatum that give rise to the direct pathway; thus dendrites and perikarya are ensheathed in afferent terminals, most of which are derived from the striatum (Figure 4(a)). They also receive a prominent afferent input on their perikarya and proximal dendrites from the GABAergic neurons of the GPe (Figure 4(b)) and glutamatergic neurons of the STN (b3 in Figures 4(a) and the labeled boutons in Figures 4(d)–(4f)). Individual basal ganglia output neurons thus receive synaptic input from both the direct pathway and the indirect pathway. The high resting discharge rate of neurons in the GPi and SNr underlies a tonic inhibition of neurons in the target regions of the basal ganglia under resting conditions. Increased activity of striatal afferents to these neurons leads to a reduction in their firing rate and hence reduced inhibition (i.e., disinhibition) of the targets of the basal ganglia. This disinhibition is considered to be a key factor in the way the basal ganglia influence behavior.

Remodeling brain cells with glucocorticoids

Dendrites (projections emanating from the neuron cell body) allow neurons to communicate with other neurons (see Figure 15.5). More and/or longer dendrites increase the opportunities for communication. Dendrites are highly plastic structures, and changes in dendrites and the synaptic contacts among neurons are also part of the physical basis of memory. Glucocorticoids have a role in dendritic remodeling. Although a stress experience that impedes performance on a memory test may shrink dendrites, an acute stress experience that improves memory performance promotes their growth. Researchers at Princeton University have examined performance on a memory task that is dependent upon the hippocampus. They have shown that acute stress improves performance on this task. Furthermore, animals that performed well on this task also had an increase in the number of dendritic spines in the hippocampus. In turn, the researchers found a direct link between the experience of stress (mild electric shocks in the feet) and increases in dendritic spines in male rats. In sum, animal studies have shown that acute stress and elevated glucocorticoid levels influence performance on memory tasks, enhancing some aspects of memory processing and impeding others, depending upon the dose of glucocorticoids and the type of memory task. In addition, stress and glucocorticoids influence the function and structure of the neural areas that are critical for memory.

There are some inconsistencies in the literature examining stress and memory in humans that are likely due to factors such as the stage of memory processing examined, pharmacological administration versus stress-induced increases in glucocorticoids, type of memory test, characteristics of the subjects (young, elderly, male, female), and so on. As a general rule, though, the effects of stress on memory that have been found in people are consistent with the findings from animal experiments. For example, a recent study at the University of Wisconsin found an inverted U-shaped relationship between performance on a recognition memory task involving both emotionally negative and neutral stimuli and glucocorticoid levels. Similarly, researchers at the University of Trier in Germany observed that either psychosocial stress or the administration of cortisol to subjects impaired performance on a declarative memory task that is highly sensitive to hippocampal function, but not on a procedural memory task that relies on structures other than the hippocampus. Findings by researchers at McGill University suggest that the prefrontal cortex and working memory may be particularly sensitive to acute elevations in cortisol levels. A curvilinear relationship was found between working memory performance and cortisol levels following the administration of various doses of hydrocortisone to young men. Thus, although not all the issues are resolved, there is evidence in people, as in experimental animals, that acute fluctuations in stress hormones influence learning and memory. In some instances, acute changes in glucocorticoid levels can improve memory function, while in others, such changes can impede memory function. The great challenge for researchers is to identify better and predict the circumstances in which acute stress will enhance or curtail performance in both people and lab animals.

Which of the following is one of the four primary goals achieved by an effective speech introduction?

Which of the following should one remember while evaluating secondary sources of information?

Which of the following strategies should be followed while developing the conclusion of a speech?

Is the study of the intended audience for a speech?