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Are there known significant (positive or negative) statistical correlations between the morphology type of neurons and the neurotransmitters that they use (presynaptic, i.e. transmitters that are released, and postsynaptic, i.e. transmitters that are received)?
This question assumes, that a definite set of morphology types has been defined. The answer depends on this definition, of course.
Yes, at least for the neurotransmitters that a given cell releases.
As far as the neurotransmitters a cell responds to, you are really better off thinking in terms of receptor expression. Most neurons will express receptors for many different neurotransmitters. It's far too broad to go into them all in an answer here.
As far as the transmitters that cells release, morphological types of neurons are very often associated with release of particular neurotransmitters. In the cortex, for example, pyramidal cells principally release glutamate while there are potentially dozens of morphological types (again, depending on how you define them) that release GABA; in the cerebellum, Purkinje neurons release GABA whereas granule cells release glutamate.
However, be careful: some terms like "granule cell" don't really refer to a special morphological type. They are really just describing "small cells in close proximity": these can be completely different types in different brain regions. It really makes no sense to ask these types of questions for the brain as a whole, you have to study individual brain regions, each of which is organized quite differently from the others.
Specialized postsynaptic morphology enhances neurotransmitter dilution and high-frequency signaling at an auditory synapse
Sensory processing in the auditory system requires that synapses, neurons, and circuits encode information with particularly high temporal and spectral precision. In the amphibian papillia, sound frequencies up to 1 kHz are encoded along a tonotopic array of hair cells and transmitted to afferent fibers via fast, repetitive synaptic transmission, thereby promoting phase locking between the presynaptic and postsynaptic cells. Here, we have combined serial section electron microscopy, paired electrophysiological recordings, and Monte Carlo diffusion simulations to examine novel mechanisms that facilitate fast synaptic transmission in the inner ear of frogs (Rana catesbeiana and Rana pipiens). Three-dimensional anatomical reconstructions reveal specialized spine-like contacts between individual afferent fibers and hair cells that are surrounded by large, open regions of extracellular space. Morphologically realistic diffusion simulations suggest that these local enlargements in extracellular space speed transmitter clearance and reduce spillover between neighboring synapses, thereby minimizing postsynaptic receptor desensitization and improving sensitivity during prolonged signal transmission. Additionally, evoked EPSCs in afferent fibers are unaffected by glutamate transporter blockade, suggesting that transmitter diffusion and dilution, and not uptake, play a primary role in speeding neurotransmission and ensuring fidelity at these synapses.
Keywords: auditory diffusion glutamate hair cell ribbon synapse synapse.
Copyright © 2014 the authors 0270-6474/14/348358-15$15.00/0.
Comparison of different afferent fiber–ribbon…
Comparison of different afferent fiber–ribbon synapse contact morphologies. A , Ribbon synapse spacing…
TBOA, a glutamate transporter blocker,…
TBOA, a glutamate transporter blocker, does not significantly alter synaptic transmission at hair…
Effects of CTZ, a blocker of AMPA receptor desensitization, on hair cell synapses.…
Spacious, spine-like synaptic connections have…
Spacious, spine-like synaptic connections have large local ECVFs that support fast synaptic glutamate…
Desensitization of fast AMPARs is…
Desensitization of fast AMPARs is highly sensitive to transmitter time course. A ,…
High-frequency release from a single…
High-frequency release from a single synapse can cause both local and spillover desensitization.…
Active transport does little to…
Active transport does little to shape rapid synaptic signaling. A , Zoomed out…
Enlarged local ECVFs enhance signaling…
Enlarged local ECVFs enhance signaling over a range of possible physiological signaling conditions.…
Comparing reliability across species with…
Comparing reliability across species with different wiring conditions. The reliability (measured as the…
The classic fight-or-flight response to perceived threat is a reflexive nervous phenomenon thai has obvious survival advantages in evolutionary terms. However, the systems that organize the constellation of reflexive survival behaviors following exposure to perceived threat can under some circumstances become dysregulated in the process. Chronic dysregulation of these systems can lead to functional impairment in certain individuals who become “psychologically traumatized” and suffer from post-traumatic stress disorder (PTSD), A body of data accumulated over several decades has demonstrated neurobiological abnormalities in PTSD patients. Some of these findings offer insight into the pathophysiology of PTSD as well as the biological vulnerability of certain populations to develop PTSD, Several pathological features found in PTSD patients overlap with features found in patients with traumatic brain injury paralleling the shared signs and symptoms of these clinical syndromes.
From energy metabolism to cognition
The brain consumes an immense amount of energy relative to the rest of the body. Thus, the mechanisms that are involved in the transfer of energy from foods to neurons are likely to be fundamental to the control of brain function. Processes that are associated with the management of energy in neurons can affect synaptic plasticity 32 ( FIG. 2 ), which could explain how metabolic disorders can affect cognitive processes. Interestingly, synaptic function can, in turn, alter metabolic energy, allowing mental processes to influence somatic function at the molecular level. BDNF is an excellent example of a signalling molecule that is intimately related to both energy metabolism and synaptic plasticity: it can engage metabolic signals to affect cognitive function 32 . BDNF is most abundant in brain areas that are associated with cognitive and metabolic regulation: the hippocampus and the hypothalamus, respectively 33 . Learning to carry out a task increases BDNF-mediated synaptic plasticity in the hippocampus 34 , 35 , and genetic deletion of the BDNF gene impairs memory formation 36 , 37 . The Met variant of the Val66Met BDNF polymorphism, a common genotype in humans that is related to abnormal trafficking and secretion of BDNF in neuronal cells 38 , is associated with abnormal hippocampal functioning and memory processing 39 . In turn, BDNF has also been shown to influence multiple parameters of energy metabolism, such as appetite suppression 40 , 41 , insulin sensitivity 42 , 43 and glucose 44 and lipid metabolism 45 . In addition, the hypothalamic melanocortin 4 receptor, which is crucial for the control of energy balance, regulates the expression of BDNF in the ventral medial hypothalamus 46 , supporting an association between energy metabolism and synaptic plasticity. In rodents, a reduction in energy metabolism caused by infusing a high dose of vitamin D3 into the brain has been shown to abolish the effects of exercise on downstream effectors of BDNF-mediated synaptic plasticity, such as calcium/calmod-ulin-dependent protein kinase II ( CaMKII ), synapsin I and cyclic AMP-responsive element (CRE)-binding protein ( CREB ) 32 . In humans, a de novo mutation in TrkB, a BDNF receptor, has been linked with hyperphagic obesity, as well as impairments in learning and memory 47 . Although energy metabolism and BDNF-mediated synaptic plasticity seem to be interconnected, further studies are crucial to determine the confines of this relationship for the modulation of cognitive function.
Diet and exercise can affect mitochondrial energy production, which is important for maintaining neuronal excitability and synaptic function. The combination of certain diets and exercise can have additive effects on synaptic plasticity and cognitive function. ATP produced by mitochondria might activate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF1), which support synaptic plasticity and cognitive function. Energy-balancing molecules, such as ubiquitous mitochondrial creatine kinase (uMtCK), AMP-activated protein kinase (AMPK) and uncoupling protein 2 (UCP2) 141 , 146 , interact with BDNF to modulate synaptic plasticity and cognition. Excess energy production caused by high caloric intake or strenuous exercise results in the formation of reactive oxygen species (ROS). When ROS levels exceed the buffering capacity of the cell, synaptic plasticity and cognitive function are compromised, probably owing to a reduction in the actions of signal-transduction modulators such as BDNF. Energy metabolism can also affect molecules such as silent information regulator 1 (SIRT1), a histone deacetylase that contributes to the reduction of ROS and promotes chromatin modifications that underlie epigenetic alterations that might affect cognition 146 . On the basis of its demonstrated susceptibility for epigenetic modification 73 , another potential target for the effects of diet on epigenetics is the BDNF gene. Two main findings support a mechanism whereby exercise, similar to diet, enhances cognitive processes through effects on energy metabolism and synaptic plasticity. First, the combination of exercise and certain diets elevates the expression of uMtCK, AMPK and UCP2, which might affect energy homeostasis and brain plasticity. Second, disruption of energy homeostasis during voluntary wheel-running abolished the effects of exercise on the actions of BDNF and BDNF end products that are important for learning and memory, suggesting that energy metabolism influences BDNF function 147 .
The mechanism whereby BDNF affects metabolism and synaptic plasticity seems to involve insulin-like growth factor 1 ( IGF1 ) 48 . IGF1 is synthesized in the liver, in skeletal muscle and throughout the brain, whereas brain IGF1 receptors are expressed mainly in the hippocampus 49 . A reduction of IGF1 signalling in rodents results in hyperglycaemia and insulin resistance, and infusion of IGF1 into the brain decreases plasma insulin levels and increases insulin sensitivity 50 . IGF1 also supports nerve growth and differentiation, neurotransmitter synthesis and release 51 and synaptic plasticity 52 , and might contribute to sustaining cognitive function after brain insults 53 , 54 , diabetes 55 and aging 56 . IGF1 has been shown in rodents to entrain similar downstream pathways to BDNF, such as the Akt signalling system 57 . Interestingly, the omega-3 fatty acid docosahexaenoic acid (DHA) stimulates neuronal plasticity through the Akt pathway 58 , suggesting that Akt activation might be crucial for integrating the effects of food-derived signals on brain plasticity. The phosphatidyl-inositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin ( mTOR ) signalling pathway seems to integrate the effects of BDNF and IGF1 on energy metabolism, synaptic plasticity, and learning and memory ( FIG. 3 ).
The omega-3 fatty acid docosahexaenoic acid (DHA), which humans mostly attain from dietary fish, can affect synaptic function and cognitive abilities by providing plasma membrane fluidity at synaptic regions. DHA constitutes more than 30% of the total phospholipid composition of plasma membranes in the brain, and thus it is crucial for maintaining membrane integrity and, consequently, neuronal excitability and synaptic function. Dietary DHA is indispensable for maintaining membrane ionic permeability and the function of transmembrane receptors that support synaptic transmission and cognitive abilities. Omega-3 fatty acids also activate energy-generating metabolic pathways that subsequently affect molecules such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF1). IGF1 can be produced in the liver and in skeletal muscle, as well as in the brain, and so it can convey peripheral messages to the brain in the context of diet and exercise. BDNF and IGF1 acting at presynaptic and postsynaptic receptors can activate signalling systems, such as the mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase II (CaMKII) systems, which facilitate synaptic transmission and support long-term potentiation that is associated with learning and memory. BDNF has also been shown to be involved in modulating synaptic plasticity and cognitive function through the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signalling pathway. The activities of the mTOR and Akt signalling pathways are also modulated by metabolic signals such as insulin and leptin (not shown). 4EBP, eukaryotic translation-initiation factor 4E binding protein CREB, cyclic AMP-responsive element (CRE)-binding protein IGFR, insulin-like growth factor receptor IRS1, insulin receptor substrate 1 p70S6K, p70 S6 kinase.
Disturbances in energy homeostasis have been linked to the pathobiology of several mental diseases, and so dietary management is becoming a realistic strategy to treat psychiatric disorders. Numerous studies have found that there might be an association between abnormal metabolism (diabetes type II, obesity and metabolic syndrome) and psychiatric disorders 59 . In a large study of patients with manic depression 60 or schizophrenia 61 , 62 , the rate of diabetes was found to be higher than in the general population (1.2% of people aged 18 years and 6.3% of people aged 45 years 163 ). The overall prevalence of diabetes in a group of 95 patients with schizophrenia was 15.8%, and this increased to 18.9% with age 61 , whereas diabetes in 203 patients with manic depression ranged from 2.9% in patients of approximately 30 years of age to 25% in patients of 75 years of age 60 . However, it is difficult to ascertain a causet relationship between diabetes and psychiatric disorders in these studies given that schizophrenia, manic depression and other psychiatric disorders are associated with poor quality of life and the side effects of anti-psychotic medication. On the basis of its effects on synaptic plasticity and energy metabolism, BDNF has been the focus of research into current hypotheses of schizophrenia and depression 63 – 66 . Low levels of BDNF in the plasma are associated with impaired glucose metabolism and type II diabetes 67 , and BDNF is reduced in the hippocampus, in various cortical areas 68 and in the serum 69 of patients with schizophrenia. In mice, genetic deletion of the TrkB receptor in the forebrain produces schizophrenic-like behaviour 70 . Furthermore, BDNF levels are reduced in the plasma of patients with major depression 71 , and chronic administration of antidepressants elevates hippocampal BDNF levels 72 . A recent study in rodents demonstrated that defeat stress, an animal model of depression, induced a lasting repression of BDNF transcripts, whereas antidepressant treatment reversed this repression by inducing histone acetylation 73 . Although the evidence is not conclusive to argue that BDNF has a role in mediating depression or schizophrenia, it is becoming clear that most treatments for depression or schizophrenia — that is, exercise and drugs — involve the action of BDNF.
Biology of Depression - Neurotransmitters
image by Patrick Hoesly (lic) Lots of research has been done on the causes of depression. We are now going to have a brief discussion of the many biological, psychological and social factors that have been identified as being related to major depressive disorder.
Biology of Depressive Disorders
You may have heard that depression is the result of a simple imbalance of brain chemicals. Although brain chemicals are certainly part of the cause, this explanation is too simple. Even just considering the biological dimension of depression, the brain has multiple layers of issues that are involved.
The brain uses a number of chemicals as messengers to communicate with other parts of itself and within the nervous system. Nerve cells are the major type of cell in the nervous system. These are called neurons. They communicate through chemical messengers, called neurotransmitters. These messengers are released and received by the brain's many neurons. Neurons are constantly communicating with each other by exchanging neurotransmitters. This communication system is essential to all of the brain's functions.
A neuron has a cell body and a tail-like structure called an axon. Neurons are spaced apart by a tiny space called a synapse. In a simple scenario, one neuron (the sender) sends a neurotransmitter message across the synapse to the next neuron (the receiver). The receiver neuron is activated by whatever chemical it just received and communicates the signal down the chain to the next neuron. The receiving end of a neuron has receptors, which receive the chemical signals. When the perfect matching signal or neurotransmitter reaches its receptor across the tiny space, the receptor is activated. It then sends the message along to the next neuron by way of a neurotransmitter. For example, if someone has to go through many locked doors with each door being behind another locked door, the right key is needed. If the first door is opened with the right key, then the person can proceed to the next door with the next key and so on.
In music, it's not just the notes that make up a melody. It is also the spaces or rests between the notes that make each note stand out and be distinct. It's exactly the same with regard to neurotransmitters and synapses. There needs to be some quiet time between neurotransmitter messages for those messages to have any meaning. It is important that receptors be allowed to reset and deactivate between messages so that they can become ready to receive the next burst of neurotransmitters. In order to achieve this "resetting", the receptors relax and release their captured neurotransmitters back into the tiny space where about 90% of them get taken up again (in a process called reuptake) by the original sending neuron. The neurotransmitters are then repackaged and reused the next time a message needs to be sent across the synapse. Even though this seems like a complicated set of steps, this entire information transmission cycle occurs in the brain within in a matter of seconds. Any problem that interrupts the smooth functioning of this chain of chemical events can negatively impact both the brain and nervous system.
Depression has been linked to problems or imbalances in the brain, specifically with the neurotransmitters serotonin, norepinephrine, and dopamine. It is very difficult to actually measure the level of neurotransmitters in a person's brain and their activity. What we do know is that antidepressant medications, which are used to treat the symptoms of depression, are known to act upon these particular neurotransmitters and their receptors. We'll talk more about antidepressant medications in the treatment section of this center.
The neurotransmitter serotonin is involved in controlling many important bodily functions, including sleep, aggression, eating, sexual behavior, and mood. Serotonin is produced by serotonergic neurons. Current research suggests that a decrease in the production of serotonin by these neurons can cause depression in some people, and more specifically, a mood state that can cause some people to feel suicidal.
In the 1960s, the "catecholamine hypothesis" was a popular explanation for why people developed depression. This hypothesis suggested that a deficiency of the neurotransmitter norepinephrine (also known as noradrenaline) in certain areas of the brain was responsible for creating depressed mood. More recent research suggests that there is a group of people with depression who have low levels of norepinephrine. Autopsy studies show that people who have experienced multiple depressive episodes have fewer norepinephrinergic neurons than people who have no depressive history. However, research results also tell us that not all people experience mood changes in response to decreased norepinephrine levels. Some people who are depressed actually show more than normal within the neurons that produce norepinephrine. More current studies suggest that in some people, low levels of serotonin trigger a drop in norepinephrine levels, which then leads to depression.
Another line of research has investigated linkages between stress, depression, and norepinephrine. Norepinephrine helps our bodies to recognize and respond to stressful situations. Researchers suggest that people who are vulnerable to depression may have a norepinephrinergic system that doesn't handle the effects of stress very efficiently.
The neurotransmitter dopamine is also linked to depression. Dopamine plays an important role in controlling our drive to seek out rewards, as well as our ability to obtain a sense of pleasure. Low dopamine levels may, in part, explain why people with depression don't get the same sense of pleasure out of activities or people that they did before becoming depressed.
In addition, new studies are showing that other neurotransmitters such as acetylcholine, glutamate, and Gamma-aminobutyric acid (GABA) can also play a role in depressive disorders. More research is necessary to understand their role in depression's brain chemistry.
Physiology and Pharmacology of Mammalian Central Neurons in Cell Culture
This chapter examines the physiology and pharmacology of mammalian central nervous system (CNS) in a sample cell culture. Current day interests in neurobiology focus on the form and function of mammalian CNS neurons the anatomic complexity of the intact mammalian CNS and the relative inaccessibility of itscellular constituents pose special difficulties for straightforward in vivo research. The study of cell cultures, that is, cultures derived from plating dissociated cells and consisting mainly of cell monolayers, of the mammalian CNS are especially appealing for detailed analysis of cellular behavior, interactions, and pharmacologic responsiveness. But there are limitations in a cell culture study: (1) variability between sets of cultures, (2) lack of the normal organization of neurons into nuclear groups composed of cells with similar synaptic and cellular properties, (3) alteration of the normal anatomic and physiologic relationship between neurons and glial cells, and (4) the relatively unknown impact of altered cellular morphology, necessitated by two dimensional growth, on synaptic integration.
Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex
Neocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs with in vivo 2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).
Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PC in vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.
How Cocaine Motivates Drug Use and Causes Addiction
Research on cocaine illustrates how a drug can disrupt neurotransmission in multiple ways to promote intensified drug use, dependence, and addiction. Like all drugs that cause dependence and addiction, cocaine alters dopamine signaling. Studies, mostly with animals, indicate that the interactions of cocaine with the dopamine and other neurotransmitter systems influence the risk of drug use, progression to addiction, and relapse after abstinence through a variety of pathways.
- Cocaine causes pleasurable feelings that motivate drug use by sharply elevating dopamine concentrations in the synapses of the reward system
- Cocaine raises synaptic dopamine levels by preventing dopamine transporters from removing dopamine from the synapse and by stimulating dopamine-releasing neurons to release dopamine that they normally hold in reserve.
- Cocaine-induced increases in dopamine signaling promote repeated cocaine use by increasing the activity of dopamine type D1 receptors in a circuit that supports the conversion of urges into action, while suppressing the activity of dopamine type D2 receptors in an opposing circuit, and by increasing the activity of dopamine type D3 receptors.
- An animal’s higher social position or exposure to a stimulating environment may limit cocaine’s power to motivate repeated use by increasing the activity of dopamine D2 receptors.
Transition to Addiction
- Cocaine sensitizes dopamine-releasing neurons in the reward system, such that repeated exposures trigger the release of increasing amounts of dopamine, potentially ratcheting up urges to use the drug again.
- The increase in dopamine-releasing neurons’ responsiveness to cocaine begins with the first exposure to the drug and even occurs with only modest doses.
- The enhanced urge for the drug with diminished control over the urge that occurs briefly following cocaine use may become an abiding state, as repeated exposure to the drug prolongs the activity imbalance in favor of urge-promoting dopamine type 1 neurons over inhibitory dopamine type 2 neurons (see also here).
- With repeated cocaine exposure, some glutamate receptors in the reward system become sensitized to cocaine cues, programming the brain to assign primary importance to reacting to the cues.
- Cocaine appears to limit the brain’s ability to alter neurotransmission pathways in response to new experiences, which potentially limits a user’s ability to develop new behavioral alternatives to drug taking.
Craving and Relapse
- , linked to the proliferation of a rare type of glutamate receptor.
- Even after extended abstinence, encounters with drug cues (i.e., things in the environment that are associated with previous drug experiences) cause dopamine to tick up in the reward system, and can rekindle powerful urges to take the drug.
- Mu opioid receptors in the frontal and temporal regions of the cortex appear to affect the intensity of a person’s craving for cocaine during his or her first few months of abstinence from the drug.
- Stress increases the likelihood that a former cocaine user’s single lapse will turn into an extended relapse because the stress hormone corticosterone augments the dopamine surge caused by cocaine
Pharmacology of Pediatric Anesthesia
Timing of Antagonists
Neurotransmission returns promptly if few receptors are blocked at the time of reversal (e.g., T 25 or when three or four twitches of TOF are present). At this stage, 70% to 75% of receptors may still be occupied ( Waud, 1971 ). Neostigmine (50 mcg/kg) is the recommended dose in infants ( Fisher et al., 1983 ). There is no clinical advantage in attempting to antagonize intense neuromuscular block (fewer than three or four twitches) in children or in administering increased doses of neostigmine or edrophonium ( Gwinnutt et al., 1991 Kopman and Eikerman, 2009 ). Data for this phenomena in children are shown in Figure 7-55 ( Meistelman et al., 1988 Donati et al., 1989 Gwinnutt et al., 1991 Bevan et al., 1999 ). The plasma level of the NMBA should be low enough that the competitive effect of the anticholinesterases allow enough muscle strength to ensure TOF of 0.9 to 1 ( Kopman et al., 1997 ). In addition, certain antibiotics, hypothermia, acidosis, hypocalcemia, and especially inhalational agents can prolong or potentiate neuromuscular block from nondepolarizing relaxants.
The present use of primarily short- and intermediate-acting relaxants may change the rule to “always reverse blockade” with AChs to “always document return of full neuromuscular function (TOF of greater than 0.9)” at the end of the case with either spontaneous or pharmacologically induced (anticholinesterases or sugammadex) recovery. Clearly, the margin of safety of relaxants is increased by using objective rather than subjective criteria to judge the adequacy of neuromuscular transmission. Experts in neuromuscular studies have documented the difficulty with subjective (visual and tactile) assessment of TOF and DBS in determining complete recovery ( Drenck, 1989 Fruergaard, 1998 ). For these reasons, an objective monitor (see Fig. 7-52 ), such as the accelerometer (AMG) is highly recommended. In addition, when objective monitoring is used, anticholinesterases can be administered at T25 (when 3 to 4 twitches are present) so that the drugs can have a complete response.
Normal Brain Development
The brain develops throughout pregnancy, and continues developing even through adolescence. During the first 10 weeks of pregnancy, the basic cells that make up the brain are formed (Figure 2). These include neurons, which eventually send electrical and chemical signals to one another, and glial cells, which provide both structural and chemical support to the neurons. During the 1st trimester, the neurons and glia undergo cell division, multiplying aggressively in preparation for their subsequent organization into specialized functions.
Figure 2: Stages of Brain Development Throughout Pregnancy
As pregnancy moves into the 2nd and 3rd trimesters, several events take place. The neurons grow, forming numerous branches (Dendrites) and an axon, structures that are crucial in sending and receiving information (Figure 3). The dendrites grow small protrusions called Spines—this increases the surface area for communication between neurons (see below). At the same time, the axons become surrounded by myelin, a fatty sheath provided by glial cells, which will help the neurons conduct electrical impulses over long distances.
Figure 3: Neuron Structure
A typical neuron is shown making a synapse with another neuron. The cell body contains the nucleus where the DNA resides. A long axon leaves the cell body and ends in a terminal. The terminal makes a connection (synapse) with the dendrites of another neuron. An enlarged view of a synapse is shown at the bottom. Within the synapse, neurotransmitters are released from the terminal of a neighboring neuron the neurotransmitters bind to specific receptors located on the dendritic spines of the receiving neuron. Receptor binding leads to either electrical or chemical signals in the receiving cell.
Once the structural aspects of neuronal development are in place, several chemical events emerge. The neurons start to synthesize their own chemicals, called Neurotransmitters. Examples include Dopamine, Serotonin, Norepinephrine, Glutamate, and γ-Aminobutyric acid (GABA). In the postnatal brain, these neurotransmitters signal neurons to perform work. The neurotransmitters are released from the terminals of axons in response to electrical signals, and they bind to special proteins called Receptors on a neighboring neuron (Figure 3).
There is a high density of these receptors on the Dendritic Spines of neurons. Each neurotransmitter binds to its own receptor serotonin binds to serotonin receptors and glutamate binds to glutamate receptors. All of this activity takes place in the Synapse or the connection between two neurons. The consequence is a change in the rate at which the receiving neuron conducts an electrical impulse. It is the rate at which neurons fire impulses within different brain regions that underlies every function in the brain, whether it is motor control, speech, learning, attention, or judgment.
However, in the developing brain, this sophisticated function of neurotransmitters is not yet needed. Instead, the neurotransmitters play a different role they serve as growth factors,directing neurons to establish connections (i.e., synapses) with appropriate neighbors bearing the corresponding receptors that will be needed for future communication.The instructions provided by the neurotransmitters and their corresponding receptors during development are crucial to the formation of functional and efficient synapses that are needed after birth.
Once the major neuronal connections are formed, there is some “pruning” that must be performed. This pruning is called Apoptosis, a genetically-programmed form of cell death. Apoptosis helps eliminate those neurons that don’t grow very well during the first two trimesters—there aren’t quite enough growth signals provided by neurotransmitters and other growth factors to reach every neuron. Thus, apoptosis ensures that any neurons that don’t grow properly are eliminated so that neuronal transmission will occur normally. Apoptosis continues well into post-natal development.
All of these developmental events progress at different rates within different brain regions. Such variation in developmental rates may explain, in part, the differential effects of alcohol, depending on when it is consumed during pregnancy.