By D. Killian. Palmer College of Chiropractic.

Stimuli delivered during bursts – short intervals of elevated spontaneous activity – were effective in modifying cortical connectivity propecia 1mg overnight delivery hair loss in neutered male cats, whereas stimuli delivered in the intervals between bursts discount propecia 1mg otc hormonal hair loss cure, though matching in number and temporal pattern, were ineffective. In all experiments, the conditioning paradigm produced a comparable degree of plasticity in the burst-triggered channels. POSSIBLE MECHANISMS FOR RAPID FLUCTUATIONS IN PLASTICITY Our preferred explanation is that neuromodulatory substances, in particular Acetyl- choline (ACh), are released in sensory cortex during the peak of the cortical © 2005 by Taylor & Francis Group. If the bursting of basal forebrain neurons causes a transient elevation in cortical ACh concentration, this could complement the increased synaptic reliability present during cortical bursts. Another candidate as a modulatory input, whose activity is linked to barrel cortex bursts, is the intralaminar thalamic nuclei. LOCUS OF MODIFICATION In awake, attentive animals, training on sensory discrimination tasks or periods of altered sensory experience cause changes in somatosensory cortical-receptive fields and cortical maps. Modification of effective intracortical connectivity has been proposed as one of the candidate mechanisms to account for the plasticity of the sensory cortex. A high level of contingency between the firing of two neurons in auditory cortex (spontaneous activity of one neuron triggered an immediate sensory input to the second neuron) altered the connectivity between the pair of neurons as measured by cross correlation. The augmented stimulus-related correlations could reflect either strengthened inter- columnar connectivity or else a more synchronized level of common ascending input to the two columns; we cannot specify the locus of this effect. In other sensory- conditioning paradigms, however, cortex is more plastic than its inputs. For example, in primates, synchronous multi-digit stimulation causes increased correlation between the neurons with paired inputs in the somatosensory cortex but not in the corresponding nucleus of the thalamus. Changes in common input synchrony specific to the paired cortical columns during spontaneous activity could occur only if the two thalamic barreloids projecting to two cortical columns were active in a more synchronous manner implying some communication between the barreloids. It is simpler to suggest that repetitive costimulation of two whiskers timed to coincide with transient increases in cortical plasticity caused the burst-conditioned, cortical barrel columns to become more strongly connected, presumably through Hebbian mechanisms. In pilot experiments, we did not detect changes in inter-columnar connectivity when recordings were made from layer IV. This, too, is consistent with the proposal that plasticity is expressed largely in lateral intracortical connections. Layer IV neurons are only weakly con- nected to neighboring columns whereas the neurons we sampled are part of a dense network of lateral connections. CONCLUDING OBSERVATIONS CONCERNING TEMPORAL PLASTICITY RULES What the present study may add to the understanding of cortical plasticity is that even in the anesthetized brain, sensory cortex can be modifiable as long as the sensory input pattern is timed to occur coincident with peaks in intrinsic fluctuations in excitability. The possibility that these findings can be of general relevance is supported by the fact that cortical fluctuations occur in every brain state. We suggest that in every state, the timing of the peaks and troughs of these variations may modulate the ability of ascending inputs to modify the cortex. In rats, intermittent fluctuations occur in relation to natural behaviors such as whisking and sniffing. We speculate that sensory information is collected and stored in the cortex at discrete time intervals dictated by such fluctuations. The earlier work concerning spatial rules suggests that when information is stored, it resides within a topographic framework – within a small set of cortical modules matching the input whiskers. Further confirmation of these ideas will require the study of unanesthetized animals. ACKNOWLEDGMENTS I thank Justin Harris, Rasmus Petersen, Stefano Panzeri, Irina Harris, Ehsan Arabza- deh, and Irina Erchova for carrying out the experiments that this review is based on. I am grateful to Miguel Maravall, and Moritz von Heimendahl for stimulating discussions related to these projects. The research discussed here has been supported by European Community IST-2000-28127, Telethon Foundation GGP02459, J. ST97, Regione Friuli Venezia Giulia, Human Frontiers Science Pro- gramme grant RGP43/2004, Wellcome Trust 066372/Z/01/Z, and The Royal Society. The description of a cortical field composed of discrete cytoarchitectonic units, Brain Res.

Opisthotonos is a convulsive condition that is often (D) Antagonism of muscarinic receptors in the associated with the ingestion of strychnine discount 1mg propecia fast delivery hair loss medication. This heart condition is associated with all of the following (E) Blockade of ganglionic transmission at sympa- EXCEPT thetic ganglia in the periphery (A) Antagonism of the inhibitory amino acid neu- rotransmitter glycine ANSWERS (B) The predominance of glycine as an inhibitory 1 cheap 1 mg propecia with mastercard hair loss video. Glycine is the major inhibitory amino acid trans- amino acid transmitter in the spinal cord mitter in the spinal cord, and strychnine is a rela- (C) Antagonism of the inhibitory amino acid neu- tively selective antagonist of glycine. Strychnine has rotransmitter GABA very little if any action at the GABA receptor– (D) The convulsions lead to tonic extension of the chloride channel complex. Which of the following classes of agents is useful tention deficit disorder are among only a few ap- in the treatment of attention deficit hyperkinetic proved uses of the psychomotor stimulants of the disorder? Analeptic stimulants, such as pentylenetetrazol (B) Benzodiazepines and picrotoxin, act by inhibiting chloride influx at (C) Xanthines the GABAA receptor–chloride channel complex. However, the concen- GABA receptor–chloride channel complex tration of cAMP that is required for such action is (B) Increased release of catecholamines from CNS above the threshold of CNS stimulation. Since the neurons methylxanthines are relatively potent antagonists of (C) Inhibition of cholinesterase leading to in- adenosine and since adenosine has been shown to creased acetylcholine levels be a reasonably potent inhibitor of both central and (D) Antagonism of CNS adrenoceptors to reduce peripheral neurons, the most likely mechanism by inhibition produced by catecholamines which CNS stimulation occurs is through antago- (E) Antagonism of nicotinic receptors that inhibit nism of adenosine receptors. The CNS stimulation produced by methylxanthines, are also indirectly acting sympathomimetics that in- such as caffeine, is most likely due to the antago- crease the release of catecholamines from sympa- nism of which of the following receptors? While amphetamine and (A) Glycine receptors other congeners possess additional actions on pe- (B) Adenosine receptors ripheral sympathetic nerves, this is the most likely (C) Glutamate receptors explanation for the cardiac stimulation observed (D) GABA receptors following the administration of these agents. Cardiac stimulation is an adverse effect associated with the use of the psychomotor stimulants, such as SUPPLEMENTAL READING amphetamine. From GABAA receptor diversity emerges a (C) Inhibition of a GABA-mediated negative unified vision of GABAergic inhibition. What types Wnessman who often spends long hours at the of pathological conditions can lead to excessive office or in his automobile traveling to meet new somnolence? Sleep apnea is characterized by pauses in the past several years, the number of daytime respiration during sleep and usually excessive snor- episodes has begun to increase, and he recently be- ing. Patients with sleep apnea have EDS but often gan to lose mobility in his arms and legs during the awake without feeling rested. Your examination re- clearly defined by determining whether he has a veals an individual who is in otherwise excellent specific human leukocyte antigen associated with health and mentation with no apparent significant the disorder (HLA-DR2). He indicates that he has several periods colepsy is accomplished with psychomotor stimu- of EDS during the day and that the frequency of lants of the amphetamine type. While he feels modafinil, pemoline, and dextroamphetamine all are well rested upon waking, he is especially concerned effective in managing the EDS periods, while about the recent loss of skeletal muscle function imipramine and clomipramine can be used to man- and fears that he may be developing some degener- age any cataplexy. Dailey DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Alprazolam 357 Lorazepam 357 Buspirone 356 Midazolam 359 Chloral hydrate 361 Oxazepam 357 Chlordiazepoxide 359 Prazepam 357 Clonazepam 359 Propranolol 361 Clorazepate 357 Temazepam 357 Diazepam 359 Triazolam 357 Flurazepam 357 Zephalon 360 Hydroxyzine 361 Zolpidem 360 The primary use of sedative–hypnotic and anxiolytic relieve symptoms of anxiety only at doses that produce drugs is to encourage calmness (anxiolytics or sedatives) noticeable sedation. All people are and relieve anxiety are consistently among the most subject to states of emotional tension and uneasiness. Whether they are pre- For otherwise healthy individuals, these occasions are scribed too frequently remains a matter of controversy. Other measures include ad- medical and surgical conditions, and it is often a symp- vice to avoid stimulants before retiring, maintenance of tom of psychiatric illness. When the symptoms become a proper diet, initiation of an exercise program, and intolerable or interfere with the treatment of the un- avoidance of stressful or anxiety-provoking situations. The ideal anxiolytic drug should calm the All central nervous system depressants have some patient without causing too much daytime sedation and ability to relieve anxiety. However, most of these drugs drowsiness and without producing physical or psycho- 355 356 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM logical dependence. Similarly, the ideal hypnotic drug Adverse Effects should allow the patient to fall asleep quickly and Like the benzodiazepines, buspirone appears to be safe should maintain sleep of sufficient quality and duration even when given in very high doses. The most common so that the patient awakes refreshed without a drug side effects are dizziness, light-headedness, and head- hangover. Abuse, dependence, and withdrawal have not been low toxicity and should not interact with other medica- reported, and buspirone administration does not pro- tions in such a way as to produce unwanted or danger- duce any cross-tolerance to the benzodiazepines.