Contents
7 Dendritic Secretion and Priming
13 Whispered Secrets and Public Announcements
List of Illustrations
Figure 3.1 The classical neuron.
Figure 3.2 Generating spikes. Neurons are electrically polarized—at rest, the electrical potential inside a neuron is about 60–70 mV negative with respect to the outside. Neurotransmitters disturb this state by opening ion channels in the membrane, allowing brief currents to flow into or out of the neuron. The inhibitory transmitter GABA opens chloride channels—these cause negatively charged chloride ions to enter the cell (chloride is much more abundant in the extracellular fluid), and this current hyperpolarizes the neuron, causing an IPSP (an inhibitory postsynaptic potential). Conversely, the excitatory neurotransmitter glutamate causes sodium channels to open, and this causes the positively charged sodium ions to enter the neuron, depolarizing it and causing an EPSP (an excitatory postsynaptic potential). If a flurry of EPSPs causes a depolarization that exceeds the neuron’s spike threshold, the neuron will fire a spike (an action potential). After a spike, neurons are typically inexcitable for a period because of a short hyperpolarizing afterpotential, and this limits how fast a neuron can fire. Trains of spikes can cause complex long-lasting changes in excitability—depolarizing afterpotentials or hyperpolarizing afterpotentials and combinations of these. These cause neurons to discharge in particular patterns of spikes. These properties vary considerably between different neuronal types.
Figure 5.1 The neuroendocrine systems of the hypothalamus. The anterior pituitary contains endocrine cells that produce six major hormones. The secretion of these hormones is controlled by “hypothalamic hormones” released by small populations of neurons in different regions of the hypothalamus. LH and FSH secretion is controlled by GnRH from neurons in the rostral hypothalamus; growth hormone secretion by GHRH from the arcuate nucleus and by somatostatin from the periventricular nucleus; prolactin secretion by dopamine from the arcuate nucleus; TSH secretion by TRH from the paraventricular nucleus; and ACTH secretion by CRF, also from the paraventricular nucleus. The posterior pituitary contains no endocrine cells: here, the two hormones oxytocin and vasopressin are secreted from the axonal endings of magnocellular neurons of the supraoptic and paraventricular nuclei. Between the posterior and anterior lobes is the intermediate lobe (not shown here). It contains cells that produce MSH, and these are directly innervated by another population of dopamine cells in the arcuate nucleus.
Figure 5.2 The milk-ejection reflex, uncovered by Wakerley and Lincoln using electrophysiological studies in anesthetized rats. In response to suckling, oxytocin cells discharge intermittently in brief synchronized bursts that evoke secretion of pulses of oxytocin, and these pulses induce abrupt episodes of milk letdown, reflected by increases in intramammary pressure. This reflex is dramatically potentiated by injections of very small amounts of oxytocin into the brain. This was the first clear demonstration that peptides, released centrally, can have potent physiological actions.
Figure 6.1 Self-priming. In gonadotrophs, LH and FSH are packaged in large dense-core vesicles. (a) shows an electron microscope image of these vesicles, which appear as small, dense, spherical objects that are scattered throughout the cell. (b) shows a reconstructed cross section of a gonadotroph, showing the nucleus (N) and the endoplasmic reticulum. In a proestrus rat, exposure of the pituitary to GnRH causes an increase in intracellular calcium that comes from the stores in the endoplasmic reticulum. This causes some LH to be secreted, but it also causes the remaining vesicles to be trafficked to sites close to the cell membrane. (c) shows the appearance of such a gonadotroph, and (d) shows a schematic reconstruction of the whole gonadotroph. Now, more of the vesicles are available to be released, so when a second GnRH challenge is given, much more LH is secreted. The graph (e) shows the resulting secretion. Redrawn from Scullion et al.
Figure 7.1 Priming in oxytocin neurons.
Figure 9.1 Kisspeptin and the GnRH neuron. The insets illustrating pulsatile secretion of GnRH and LH on the left and surge secretion on the right are adapted from published work of Sue Moenter, Alain Caraty, Alain Locatelli, and Fred Karsch, showing that “GnRH secretion leading up to ovulation in the ewe is dynamic, beginning with slow pulses during the luteal phase, progressing to higher frequency pulses during the follicular phase and invariably culminating in a robust surge of GnRH.”
Figure 10.1 Phasic firing in vasopressin neurons. Magnocellular vasopressin neurons secrete vasopressin into the blood from the swellings and nerve endings of axons in the posterior pituitary gland. This secretion is governed by the spike activity of the neurons. The spike activity can be monitored by a microelectrode whose tip is placed either inside a vasopressin cell (intracellular recording) or just outside the cell (extracellular recording). These neurons discharge spikes in long bursts of activity separated by long silences. Intracellular recordings made in vitro have revealed the mechanisms underlying these bursts, and one early key observation, shown here, is that the bursts of spikes “ride” upon a plateau of depolarization that is the result of a depolarizing afterpotential. The mechanisms have been reconstructed in computational models of vasopressin cells, and the traces on the left are simulations of the activity of a vasopressin neuron in response to increasing osmotic stimulation. The graph on the right shows measurements of vasopressin in rat blood, and it shows how the vasopressin concentration is linearly related to the plasma osmotic pressure.
Figure 10.2 Bistability. Bistability in neurons can arise from a positive feedback mechanism that saturates: spike activity in vasopressin cells produces a depolarizing afterpotential that increases neuronal excitability, but its effect saturates because short hyperpolarizing afterpotentials after each spike limit how fast the neuron can fire. Bistable oscillations arise because of a slower activity-dependent inhibition—the afterhyperpolarization. This can be mimicked by two differential equations challenged by a “noisy” input mimicking synaptic input. Here, v represents neuronal activity and w represents activity-dependent inhibition; this system alternates between “bursts” and “silences.” In such a system, perturbations can have paradoxical effects. (a) shows the system “firing phasically” in response to a constant, noisy input (vsyn). (b) Here, the input is the same as in (a), but at the arrow a brief additional excitation stops the first burst. (c) The same effect occurs with a brief inhibition (open arrow). (d) Here, a brief excitation given in a silent period triggers a burst, and (e) a brief inhibition at the same time also triggers a burst.
Figure 10.3 Heterogeneity. Vasopressin cells all fire in different patterns—the examples on the left show some of the different types of patterns in which different neurons fire at any given time. The neurons also vary in their mean firing rate and in their sensitivity to osmotic pressure. The mechanisms of phasic firing and the heterogeneity of neurons were modeled by Duncan MacGregor, who also modeled the pattern of vasopressin secretion from each cell. On the right is the modeled average secretion from 100 different vasopressin cells as a function of the average synaptic input to the population. Secretion from each one is very nonlinear, but the total secretion from the population, shown as the heavy black line, is linearly proportional to the input rate.
Figure 14.1 Amplification and feedback in the stress axis. In the rat, CRF (and vasopressin) is produced in about 1,000 neuroendocrine neurons of the paraventricular nucleus. These neurons project to the median eminence, where they release brief pulses of CRF into portal blood vessels that carry the CRF to the anterior pituitary. There, CRF stimulates the corticotrophs to secrete pulses of ACTH, which reaches levels of up to 1 ng/ml in the blood. ACTH acts on about 400,000 cells of the adrenal cortex to stimulate the production of corticosterone, which reaches levels of 80 ng/ml and more in plasma. This acts back on both the pituitary and the brain. The secretion of corticosterone follows a diurnal rhythm—rats are nocturnal, and highest levels occur at about the time they become active. This daily rhythm is governed by light signals, detected by the retina and communicated to the paraventricular nucleus via the suprachiasmatic nucleus. Illustration modified from Spiga F et al.
Figure 16.1 Trends in food intake. Data collected by an annual survey of food purchases in the United Kingdom. From 1940 to 1973, the data did not include alcoholic drinks, soft drinks, confectionery, or eating out. From 1973 to 1991, the reported intakes were adjusted. From 1992 onward the data included alcoholic drinks, soft drinks, and confectionery, and from 1994 they also included eating out. The data (https://www.gov.uk/government/collections/family-food-statistics/) were published on March 9, 2017, by the Department for Environment, Food, and Rural Affairs in the UK. Data were collected annually for a sample of households using self-reported diaries of all purchases over a two-week period. Where possible, quantities were recorded in the diaries, but otherwise they were estimated. Energy and nutrient intakes were calculated using standard nutrient composition data for each of 500 food types.