Medial Reticular Formation Research Articles

Development of the Vestibular Apparatus and Central Vestibular Connections in a Wallaby (Macropus eugenii)

We have studied the early development of the vestibular apparatus and its central connections in the tammar wallaby (Macropus eugenii) in order to determine whether the vestibular system anatomy is sufficiently mature at birth to assist in climbing to the pouch. Structural development was studied with the aid of hematoxylin and eosin stained sections and immunoreactivity for GAP-43, whereas the development of vestibular system connections was examined by carbocyanine dye tracing. At the time of birth, the otocyst has distinct utricle, saccule and semicircular canals with immature sensory regions receiving innervation by GAP-43 immunoreactive fibers. Vestibular nerve fibers can be traced into the brainstem to the developing vestibular nuclei, which are not yet cytoarchitectonically distinct. The vestibular nuclei do not contribute direct projections to the lower cervical spinal cord at birth; most bulbospinal projections in the newborn appear to be derived bilaterally from the gigantocellular, lateral paragigantocellular reticular and ventral medullary nuclei. A substantial bilateral projection to the vestibular ganglion and apparatus from the region of the gigantocellular and lateral paragigantocellular nuclei was seen at birth, but not in subsequent ages. This is similar to a projection seen in newborn Ameridelphians. By postnatal day (P) 5, the vestibular apparatus had extensive projections to all vestibular nuclei and neurons projecting in the lateral vestibulospinal tract could be identified in the lateral vestibular nucleus. Cytoarchitectonic differentiation of the vestibular nuclei proceeded over the next 3 to 4 weeks with the emergence of discrete parvicellular and magnocellular components of the medial vestibular nucleus by P19. GAP-43 immunoreactivity stayed high in the lateral vestibulospinal tract for several months after birth, suggesting that the development of this tract followed a prolonged timecourse. Our findings indicate that central and peripheral connections of the vestibular ganglion are present at birth, but that there is no direct projection from the vestibular nuclei to the cervical spinal cord until P5. Nevertheless, the possibility remains that an indirect projection between the vestibular nuclei and the medial reticular formation is present at birth and mediates control of the climb.

Arousal of cerebral cortex electroencephalogram consequent to high-frequency stimulation of ventral medullary reticular formation

We have theorized that large neurons in the ventral and medial reticular formation of the medulla are critical for both autonomic and cortical arousal. To test this theory, we anesthetized rats with urethane, lowered concentric bipolar stimulating electrodes into the medullary reticular formation, and implanted electroencephalogram (EEG) and ECG recording electrodes. We stimulated in the medulla with pulse frequencies ranging from 50 to 300 Hz while recording cortical EEG and ECG. These female rats were ovariectomized, and one subgroup was administered estradiol. Electrical stimulation at either 200 or 300 Hz among the large medullary reticular neurons in nucleus paragigantocellularis (PGi) caused a significant reduction in the portion of the EEG power spectrum represented by delta-waves (0.1-4 Hz) and -waves (4.1-8 Hz). Correspondingly, there were increases in gamma-wave power (22-50 Hz), especially when using 300 Hz. Stimulation at </=100 Hz produced fewer changes in cortical EEG. The major features of these results were not significantly different according to estradiol treatment. In contrast, estradiol administration significantly lowered ECG. Electrical stimulation in PGi increased ECG in vehicle control animals, but decreased it in estradiol-treated animals. Regarding the EEG, we conclude that, even in anesthetized animals, stimulation of PGi reticular neurons can increase cortical arousal and that high frequencies of stimulation amplify this effect.

Localization of calcium-binding protein (calretinin, 29 kD) in the brain and pituitary gland of teleost fish: An immunohistochemical study

Immunocytochemical techniques were used to investigate the distribution of calretinin in the brain and pituitary gland of the hardhead catfish Arius felis. Calretinin immunoreactive neurons were found in the telencephalon (lateral nucleus of ventral telencephalic area), diencephalon (around the medial forebrain bundle, lateral tuberal nucleus, central pretectal nucleus, posterior periventricular hypothalamic nucleus, medial preglomerular nucleus, diffuse nucleus of the inferior lobe), mesencephalon (nucleus of the medial longitudinal fascicle, ventral nucleus of the semicircular torus), cerebellum (valvula cerebelli, eurydendroid cells) and rhombencephalon (secondary gustatory nucleus, isthmic nucleus, trigeminal motor nucleus, medial auditory nucleus of the medulla, medial and inferior reticular formation, anterior, descending, posterior and tangential octaval nuclei). Calretinin-labeled fibers were observed in the optic nerve and at the levels of the central pretectal nucleus, the nucleus of the medial longitudinal fascicle, the ventral nucleus of the semicircular torus, the secondary gustatory nucleus, the trigeminal motor nucleus, the eurydendroid cells, the medial auditory nucleus of the medulla and the octaval nucleus. For the first time, we are reporting on calretinin-positive cells in the rostral and proximal pars distalis of the adenohypophysis. Although, it seems speculatory, calretinin-expressing cells in the pituitary gland may be involved in hormonal regulation and hence, calretinin might play a significant role in governing hypophysial functions in fishes. Our results suggest that calretinin shows species-specific variations also among the teleost fish, similar to mammals.

Is there a brainstem substrate for action selection?

The search for the neural substrate of vertebrate action selection has focused on structures in the forebrain and midbrain, and particularly on the group of sub-cortical nuclei known as the basal ganglia. Yet, the behavioural repertoire of decerebrate and neonatal animals suggests the existence of a relatively self-contained neural substrate for action selection in the brainstem. We propose that the medial reticular formation (mRF) is the substrate's main component and review evidence showing that the mRF's inputs, outputs and intrinsic organization are consistent with the requirements of an action-selection system. The internal architecture of the mRF is composed of interconnected neuron clusters. We present an anatomical model which suggests that the mRF's intrinsic circuitry constitutes a small-world network and extend this result to show that it may have evolved to reduce axonal wiring. Potential configurations of action representation within the internal circuitry of the mRF are then assessed by computational modelling. We present new results demonstrating that each cluster's output is most likely to represent activation of a component action; thus, coactivation of a set of these clusters would lead to the coordinated behavioural response observed in the animal. Finally, we consider the potential integration of the basal ganglia and mRF substrates for selection and suggest that they may collectively form a layered/hierarchical control system.

Forced Moves or Good Tricks in Design Space? Landmarks in the Evolution of Neural Mechanisms for Action Selection

This review considers some important landmarks in animal evolution, asking to what extent specialized action-selection mechanisms play a role in the functional architecture of different nervous system plans, and looking for “forced moves” or “good tricks” (see Dennett, D., 1995, Darwin’s Dangerous Idea, Penguin Books, London) that could possibly transfer to the design of robot control systems. A key conclusion is that while cnidarians (e.g. jellyfish) appear to have discovered some good tricks for the design of behavior-based control systems—largely lacking specialized selection mechanisms—the emergence of bilaterians may have forced the evolution of a central ganglion, or “archaic brain”, whose main function is to resolve conflicts between peripheral systems. Whilst vertebrates have many interesting selection substrates it is likely that here too the evolution of centralized structures such as the medial reticular formation and the basal ganglia may have been a forced move because of the need to limit connection costs as brains increased in size.

Mapping the spinal and supraspinal pathways of dynamic mechanical allodynia in the human trigeminal system using cardiac-gated fMRI

Following injury and inflammation, pain to light stroking (dynamic mechanical allodynia) might develop at the damaged site (primary area) or in adjacent normal tissue (secondary area).Using fMRI we mapped changes in the spinal trigeminal nucleus (spV), and supraspinal brainstem nuclei following heat/capsaicin-induced primary and secondary dynamic mechanical allodynia in the human trigeminal system. The role of these structures in dynamic mechanical allodynia has not been clarified yet in humans. During the control session we applied the same mechanical stimuli to the same untreated trigeminal area.Primary and secondary mechanical allodynia showed equal levels of perceived pain intensity, and compared to control mechanical stimulation exhibited similar responses in the ipsilateral spV and contralateral ventrolateral periaqueductal gray (vlPAG). Activity in the spV was significantly higher during both conditions versus the control mechanical stimulation, indicating that central sensitization of second-order neurons is similar for primary and secondary mechanical allodynia. The vlPAG showed decreased activity that inversely correlated with pain ratings during primary allodynia, i.e. the more deactivated the vlPAG the higher the pain intensity (p<0.05, Pearson's correlation).Primary and secondary dynamic mechanical allodynia were also characterized by significant differences involving distinct supraspinal structures mainly involved in pain modulation and including the rostroventromedial medulla, pons reticular formation, dorsolateral PAG, all more active during primary versus secondary allodynia, and the medial reticular formation of the caudal medulla that was more active during secondary versus primary allodynia. These results indicate that the pain modulatory system is involved to a different extent during primary versus secondary mechanical allodynia.

Who dominates who in the dark basements of the brain?

Subcortical substrates for behavioural integration include the fore/midbrain nuclei of the basal ganglia and the hindbrain medial reticular formation. The midbrain superior colliculus requires basal ganglia disinhibition in order to generate orienting movements. The colliculus should therefore be seen as one of many competitors vying for control of the body's effector systems with the basal ganglia acting as the key arbiter.

Taste‐evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat

The current investigation used double labeling for NADPHd and Fos-like immunoreactivity to define the relationship between nitric oxide synthase-containing neural elements and taste-activated neurons in the nucleus of the solitary tract (NST) and subjacent reticular formation (RF). Stimulation of awake rats with citric acid and quinine resulted in significant increases in the numbers of double-labeled neurons in both the NST and RF, suggesting that some medullary gustatory neurons utilize nitric oxide (NO) as a transmitter. Overall, double-labeled neurons were most numerous in the caudal reaches of the gustatory zone of the NST, where taste neurons receive inputs from the IXth nerve, suggesting a preferential role for NO neurons in processing gustatory inputs from the posterior oral cavity. However, double-labeled neurons also exhibited a preferential distribution depending on the gustatory stimulus. In the NST, double-labeled neurons were most numerous in the rostral central subnucleus after either stimulus but had a medial bias after quinine stimulation. In the RF, after citric acid stimulation, there was a cluster of double-labeled neurons with distinctive large soma in the parvicellular division of the lateral RF, subjacent to the rostral tip of NST. In contrast, in response to quinine, there was a cluster of double-labeled neurons with much smaller soma in the intermediate zone of the medial RF, a few hundred micrometers caudal to the citric acid cluster. These differential distributions of double-labeled neurons in the NST and RF suggest a role for NO in stimulus-specific gustatory autonomic and oromotor reflex circuits.

Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in cat modulate acetylcholine release in pontine reticular formation

ACh regulates arousal, and the present study was designed to provide insight into the neurochemical mechanisms modulating ACh release in the pontine reticular formation. Nitric oxide (NO)-releasing beads microinjected into the pontine reticular formation of C57BL/6J (B6) mice significantly (P < 0.0001) increased ACh release. Microdialysis delivery of the NO donor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC-12) to the mouse pontine reticular formation also caused a concentration-dependent increase in ACh release (P < 0.001). These are the first neurochemical data showing that ACh release in the pontine reticular formation of the B6 mouse is modulated by NO. The signal transduction cascade through which NO modulates ACh release in the pontine reticular formation has not previously been characterized. Therefore, an additional series of studies quantified the effects of a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), on ACh release in the cat medial pontine reticular formation. During naturally occurring states of sleep and wakefulness, but not anesthesia, ODQ caused a significant (P < 0.001) decrease in ACh release. These results show for the first time that NO modulates ACh in the medial pontine reticular formation of the cat via an NO-sensitive sGC signal transduction cascade. Isoflurane and halothane anesthesia have been shown to decrease ACh release in the medial pontine reticular formation. The finding that ODQ did not alter ACh release during isoflurane or halothane anesthesia demonstrates that these anesthetics disrupt the NO-sensitive sGC-cGMP pathway. Considered together, results from the mouse and cat indicate that NO modulates ACh release in arousal-promoting regions of the pontine reticular formation via an NO-sensitive sGC-cGMP pathway.

Morphological and immunohistochemical characterization of interneurons within the rat trigeminal motor nucleus

Three series of experiments were carried out to characterize interneurons located within the trigeminal motor nucleus of young rats aged 5–24 days. Cholera toxin injections were made bilaterally into the masseter and, sometimes, digastric muscles to label motoneurons. In the first set of experiments, thick slices were taken from the pontine brainstem and cholera toxin-positive and cholera toxin-negative neurons located inside the trigeminal motor nucleus were filled with biocytin through whole-cell recording patch electrodes. Positively identified motoneurons (cholera toxin+) of various shapes and sizes always had a thick, unbranched axon that entered the motor root following a tight zigzag course. Many cholera toxin-negative neurons were also classified as motoneurons after biocytin filling based on this particularity of their axon. These are probably either fusimotor motoneurons or motoneurons supplying other jaw muscles. The cholera toxin-negative neurons classified as interneurons differed markedly from motoneurons in that they had thin, usually branched axons that supplied the ipsilateral reticular region surrounding the trigeminal motor nucleus (peritrigeminal area), the main trigeminal sensory nucleus, the trigeminal mesencephalic nucleus, the medial reticular formation of both sides, and the contralateral medial peritrigeminal area. Most often, their dendrites were arranged in bipolar arbors that extended beyond the borders of the trigeminal motor nucleus into the peritrigeminal area. Immunohistochemistry against glutamate, GABA and glycine was used to further document the nature and distribution of putative interneurons. Immunoreactive neurons were uniformly distributed throughout the rostro-caudal extent of the trigeminal motor nucleus. Their concentration seemed greater toward the edges of the nucleus and they were scarce in the digastric motoneuron pool. Glutamate- outnumbered GABA- and glycine-immunoreactive neurons. There was no clear segregation between the three populations. In the final experiment, 1,1′-dioctadecyl-3,3,3′,3′-tetra-methylindocarbocyanine perchlorate crystals were inserted into one trigeminal motor nucleus in thick slices and allowed to diffuse for several weeks. This procedure marked commissural fibers and interneurons in the contralateral trigeminal motor nucleus. Together these results conclusively support the existence of interneurons in the trigeminal motor nucleus.

The brainstem reticular formation is a small-world, not scale-free, network

Recently, it has been demonstrated that several complex systems may have simple graph-theoretic characterizations as so-called 'small-world' and 'scale-free' networks. These networks have also been applied to the gross neural connectivity between primate cortical areas and the nervous system of Caenorhabditis elegans. Here, we extend this work to a specific neural circuit of the vertebrate brain--the medial reticular formation (RF) of the brainstem--and, in doing so, we have made three key contributions. First, this work constitutes the first model (and quantitative review) of this important brain structure for over three decades. Second, we have developed the first graph-theoretic analysis of vertebrate brain connectivity at the neural network level. Third, we propose simple metrics to quantitatively assess the extent to which the networks studied are small-world or scale-free. We conclude that the medial RF is configured to create small-world (implying coherent rapid-processing capabilities), but not scale-free, type networks under assumptions which are amenable to quantitative measurement.

Identification of roughskin newt medullary vasotocin target neurons with a fluorescent vasotocin conjugate

Arginine8 vasotocin (AVT), a neurohypophyseal peptide in nonmammalian vertebrates, plays a key role in the regulation of social behaviors related to reproduction. In male roughskin newts (Taricha granulosa), AVT is an important facilitator of several reproductive behaviors, including courtship clasping of females. Although AVT is known to act in certain brain regions and AVT receptors have been localized to some extent, specific target neurons for this peptide have not been identified in any species. Internalization of a receptor-specific conjugate of AVT and the fluorescent dye Oregon green was used to identify AVT target cells in the medulla of male roughskin newts. Medullary neurons are of interest because they appear to mediate facilitation of clasping by AVT. Direct application of AVT-Oregon green to the fourth ventricular surface of the medulla in vivo resulted in conjugate internalization by a widespread population of medullary neurons, particularly in the medial reticular formation and nuclei of cranial nerves V, VII, VIII, IX, and X. Some fourth-ventricle ependymal cells were also labeled. Reticulospinal neurons, which play an important role in clasping, were identified by retrograde labeling with tetramethylrhodamine dextran amine. AVT-Oregon green was internalized by 72% of these neurons. These results show that AVT can directly affect a very large and diverse medullary neuronal population, which may underlie the peptide's role in multiple neuroendocrinological processes, including autonomic and behavioral regulation. Selectivity of the AVT action may arise through interactions between AVT and steroids such as corticosterone.

ATP-sensitive and voltage-dependent potassium channel involved in the antinociceptive effects produced by an adenosine A1 agonist into the brainstem medial pontine reticular formation in rats

Department of Anesthesiology of Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing, China

Electrophysiological and morphological properties of identified crossed tecto-reticular neurons in the rat superior colliculus

Previously we classified randomly sampled neurons in the intermediate layer (SI) of the rat superior colliculus (SC) into six subclasses according to their firing responses to depolarizing current pulses and five subclasses based on their morphological properties in slice preparations. In the present study, we investigated properties of a major output cell group of the rat SC (PND 17–24), crossed tecto-reticular neurons (cTRNs), which project to the contralateral medial pontine reticular formation. The cTRNs were identified by retrograde labeling with a fluorescent tracer ( n = 112). We compared their properties with those of presumed interneurons ( n = 127). We found that a majority of cTRNs were regular spiking neurons with moderate firing frequency (73%) and were multipolar-shaped (66%). The cTRNs had larger membrane capacitance, larger soma size and lower input impedance than presumed interneurons. Electrical stimulation of the superficial gray layer induced oligosynaptic EPSPs in the cTRNs. When bicuculline was added to the extracellular solution, the EPSPs were markedly enhanced and bursting spike responses were induced. The bursting responses were suppressed by applying d-2-amino-5-phosphonovalerate. These results suggest that the cTRNs exhibit NMDA receptor-dependent bursting responses to visual inputs. These observations give insights into the neuronal mechanism of generating burst activity in cTRNs, which triggers orienting behaviors.

Reticulo-collicular projections: a neuronal tracing study in the rat

Neuroanatomical tract-tracing methods were used to study the topography of the reticulocollicular projections. Injections of gold-HRP or BDA tracers into the medial and/or central portions of the superior colliculus resulted in labelled neurones mainly in the medial reticular formation, whereas injections into the lateral portion of the superior colliculus showed labelling in the medial and lateral reticular formation. When tracer was injected into the lateral portion of the caudal superior colliculus, extensive lateral labelling was observed in the contralateral parvocellular reticular nucleus and the contralateral dorsal medullary reticular nucleus, two areas involved in reflex blinking. The present study shows that these reticular areas project to the lateral superior colliculus, which is known to be involved in the coordination of eye and eyelid movements.

GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridization.

Electron microscopy suggests that up to half the synaptic input to sympathetic preganglionic neurons (SPGNs) is GABAergic or glycinergic. A proportion of this input is suspected to originate from neurons located within the medulla oblongata. The present study provides definitive evidence for the existence of these supraspinal presympathetic (PS) neurons with inhibitory phenotypes. PS neurons were identified by retrograde trans-synaptic migration of pseudorabies virus (PRV) injected into the adrenal gland. GABAergic or glycinergic cell bodies were identified by the presence of glutamate decarboxylase (GAD)-67 mRNA or glycine transporter (GlyT)-2 mRNA detected with in situ hybridization (ISH). Neither GABAergic nor glycinergic PS neurons were tyrosine hydroxylase (TH)-immunoreactive (ir). GABAergic PS neurons were located within the ventral gigantocellular nucleus, gigantocellular nucleus alpha, and medial reticular formation, mostly medial to the TH-ir PS neurons. About 30% of GABAergic PS neurons were serotonergic cells located in the raphe pallidus (RPa) and parapyramidal region (PPyr). Glycinergic PS neurons had the same general distribution as the GABAergic cells, except that no glycinergic neurons were located in the RPa or PPyr and none were serotonergic. PRV immunohistochemistry combined with ISH for both GlyT2 and GAD-67 mRNAs showed that at least 63% of midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic PS neurons were GABAergic. In conclusion, the rostral ventromedial medulla contains large numbers of GABAergic and glycinergic neurons that innervate adrenal gland SPGNs. Over half of these PS neurons may release both transmitters. The physiological role of this medullary inhibitory input remains to be explored.

Immunohistochemical distribution of tachykinins in the CNS of the lamprey Petromyzon marinus.

The presence of tachykinins in the CNS of vertebrates has been known for many decades, and numerous studies have described their distribution in mammals. Tachykinins were also reported in the CNS of lampreys using immunohistochemistry, chromatography, and radioimmunoassay methods, but the use of substance P (SP)-specific antibodies to reveal those tachykinins could have led to an underestimation of their number in this genus. Therefore, we carried out a new immunohistochemical study on Petromyzon marinus using a commercial polyclonal antibody that binds not only to mammalian SP, but also to other neurokinins. This antibody labeled all previously described lamprey tachykinin-containing neuronal populations, but more important, labeled new populations in several parts of the brain. These include the dorsal gray of the rostral spinal cord, the dorsal column nuclei, the octavolateral area, the nucleus of the solitary tract, the medial rhombencephalic reticular formation, the lateral tegmentum of the rostral rhombencephalon, the torus semicircularis, the optic tectum, the habenula, the mammillary area, the dorsal thalamic area, the lateral hypothalamus, and the septum area. Preabsorption experiments confirmed the binding of the antibody to neurokinins and allowed us to propose that the CNS of P. marinus contains at least two different tachykinins.

Responses of feline medial medullary reticular formation neurons with projections to the C 5–C 6 ventral horn to vestibular stimulation

Prior studies have shown that the vestibular system contributes to adjusting respiratory muscle activity during changes in posture, and have suggested that portions of the medial medullary reticular formation (MRF) participate in generating vestibulo-respiratory responses. However, there was previously no direct evidence to demonstrate that cells in the MRF relay vestibular signals monosynaptically to respiratory motoneurons. The present study tested the hypothesis that the firing of MRF neurons whose axons could be antidromically activated from the vicinity of diaphragm motoneurons was modulated by whole-body rotations in vertical planes that stimulated vestibular receptors, as well as by electrical current pulses delivered to the vestibular nerve. In total, 171 MRF neurons that projected to the C 5–C 6 ventral horn were studied; they had a conduction velocity of 34±15 (standard deviation) m/sec. Most (135/171 or 79%) of these MRF neurons lacked spontaneous firing. Of the subpopulation of units with spontaneous discharges, only 3 of 20 cells responded to vertical rotations up to 10° in amplitude, whereas the activity of 8 of 14 neurons was affected by electrical stimulation of the vestibular nerve. These data support the hypothesis that the MRF participates in generating vestibulo-respiratory responses, but also suggest that some neurons in this region have other functions.

Motor outputs from the primate reticular formation to shoulder muscles as revealed by stimulus-triggered averaging.

The motor output of the medial pontomedullary reticular formation (mPMRF) was investigated using stimulus-triggered averaging (StimulusTA) of EMG responses from proximal arm and shoulder muscles in awake, behaving monkeys (M. fascicularis). Muscles studied on the side ipsilateral (i) to stimulation were biceps (iBic), triceps (iTri), anterior deltoid (iADlt), posterior deltoid (iPDlt), and latissimus dorsi (iLat). The upper and middle trapezius were studied on the ipsilateral and contralateral (c) side (iUTr, cUTr, iMTr, cMTr). Of 133 sites tested, 97 (73%) produced a poststimulus effect (PStE) in one or more muscles; on average, 38% of the sampled muscles responded per effective site. For responses that were observed in the arm and shoulder, poststimulus facilitation (PStF) was prevalent for the flexors, iBic (8 responses, 100% PStF) and iADlt (13 responses, 77% PStF), and poststimulus suppression (PStS) was prevalent for the extensors, iTri (22 responses, 96% PStS) and iLat (16 responses, 81% PStS). For trapezius muscles, PStS of upper trapezius (iUTr, 49 responses, 73% PStS) and PStF of middle trapezius (iMTr, 22 responses, 64% PStF) were prevalent ipsilaterally, and PStS of middle trapezius (cMTr, 6 responses, 67% PStS) and PStF of upper trapezius (cUTr, 46 responses, 83% PStS) were prevalent contralaterally. Onset latencies were significantly earlier for PStF (7.0 +/- 2.2 ms) than for PStS (8.6 +/- 2.0 ms). At several sites, extremely strong PStF was evoked in iUTr, even though PStS was most common for this muscle. The anatomical antagonists iBic/iTri were affected reciprocally when both responded. The bilateral muscle pair iUTr/cUTr demonstrated various combinations of effects, but cUTr PStF with iUTr PStS was prevalent. Overall, the results are consistent with data from the cat and show that outputs from the mPMRF can facilitate or suppress activity in muscles involved in reaching; responses that would contribute to flexion of the ipsilateral arm were prevalent.

Cholinergic mechanisms mediating anesthetic induced altered states of consciousness

A host of central neurotransmitter systems subserving γ -aminobutyric acid (GABA)ergic, glutamatergic, adrenergic, serotonergic, and cholinergic transmission are likely affected by anesthetics. Anesthetic drugs interfere with cholinergic processes associated with altered states of consciousness. For example, administration of opiates, halothane, isoflurane, and enflurane are associated with decreased acetylcholine (ACh) release from neurones in the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei projecting to the medial pontine reticular formation. Conversely, drugs that directly affect cholinergic activity also influence minimum alveolar concentration (MAC). There is one possibility that general anesthetics interfere directly with cholinergic transmission to produce unconsciousness. A series of experiments presented focuses on a hypothesis that the loss of consciousness produced by anesthetic drugs involves depression, directly or indirectly, of central cholinergic transmission. It was investigated whether physostigmine, a centrally-acting anticholinesterase, reverses the loss of consciousness produced by continuous administration of anesthetic drugs. In addition, it was determined whether the reversal was blocked by scopolamine, a nonselective centrally-acting muscarinic antagonist.