bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Control of Leg Movements and Motor Patterns during Grooming in Locusts
Authors: Berkowitz Ari , Laurent Gilles
Published: April 2018

This study demonstrates that the thoracic and abdominal nervous system of locusts is sufficient to mediate several site-specific and distinct grooming leg movements. Locusts can use a hindleg or middle leg to groom at least four ipsilateral thoracic and abdominal sites, without input from the brain, subesophageal ganglion, or prothoracic ganglion. The hindleg is used to groom the posterior abdomen, the ventral or posterior hindleg coxa, and the ear; the middle leg is used to groom the anterior hindleg coxa. Grooming movements are often rhythmic and display site-specific intralimb coordination patterns. During grooming of the posterior abdomen or ventral hindleg coxa, for example, hindleg tibial extension occurs nearly simultaneously with femur elevation, in contrast with locust hindleg movements during walking. Electromyographic (EMG) recordings during these movements show that rhythmic bursts of tibial extensor activity occur nearly in-phase with those of trochanteral levators, in contrast to hindleg EMGs during walking. During grooming of the ear, hindleg tibial extension/flexion and tibial extensor/flexor muscle bursts can occur independently of the femur elevation/depression and trochanteral levator/depressor muscle bursts, suggesting that the neural modules controlling tibial and femoral movements can be uncoupled during this behavior. Tibial extension can occur before, or even in the absence of, tibial extensor muscle activity, suggesting that spring-like properties of the leg and energy transfer from femur motion may play important roles in such leg movements. Adjacent legs sometime show coordinated femur movement during grooming with one hindleg, suggesting that grooming may also involve interlimb coordination.
Central Generation of Grooming Motor Patterns and Interlimb Coordination in Locusts
Authors: Berkowitz Ari , Laurent Gilles
Published: April 2018

Coordinated bursts of leg motoneuron activity were evoked in locusts with deefferented legs by tactile stimulation of sites that evoke grooming behavior. This suggests that insect thoracic ganglia contain central pattern generators for directed leg movements. Motoneuron recordings were made from metathoracic and mesothoracic nerves, after eliminating all leg motor innervation, as well as all input from the brain, subesophageal ganglion, and prothoracic ganglion. Strong, brief trochanteral levator motoneuron bursts occurred, together with silence of the slow and fast trochanteral depressor motoneurons and activation of the common inhibitor motoneuron. The metathoracic slow tibial extensor motoneuron was active in a pattern distinct from its activity during walking or during rhythms evoked by the muscarinic agonist pilocarpine. Preparations in which the metathoracic ganglion was isolated from all other ganglia could still produce fictive motor patterns in response to tactile stimulation of metathoracic locations. Bursts of trochanteral levator and depressor motoneurons were clearly coordinated between the left and right metathoracic hemiganglia and also between the mesothoracic and the ipsilateral metathoracic ganglia. These data provide clear evidence for centrally generated interlimb coordination in an insect.
Amiloride Disrupts NaCl versus KCl Discrimination Performance: Implications for Salt Taste Coding in Rats
Authors: Spector Alan C. , Guagliardo Nick A. , St. John Steven J.
Published: April 2018

Amiloride, an epithelial sodium channel blocker, suppresses the responsiveness of narrowly tuned sodium-responsive taste afferents when orally applied in the rat. Broadly tuned salt-responsive taste afferents, which respond to sodium and nonsodium salts and acids, are relatively unaffected by the drug. We used amiloride treatment to examine the consequences of the specific removal of input from narrowly tuned sodium-responsive afferents on taste discrimination. Five water-restricted rats were trained in a gustometer to press one lever after licking NaCl and another lever after licking KCl across a range of concentrations (0.05, 0.1, and 0.2m). Correct responses were rewarded with brief water access, and incorrect responses were punished with a time-out. After training, animals averaged about 90% correct responses and maintained competent performance during subsequent control sessions. Amiloride was then placed in all solutions at a given concentration (1–100 μm) for single test sessions. Control sessions were interposed between amiloride sessions. At high amiloride concentrations, overall responding was reduced to 50% correct and progressively improved as the drug concentration was lowered. The sigmoidal dose–response functions corresponded quantitatively with electrophysiological findings. Performance deficits occurred primarily with NaCl and were concentration dependent; performance during KCl trials was relatively undisturbed by amiloride adulteration. At high amiloride concentrations, rats treated NaCl as if it were KCl. Given that amiloride is tasteless to the rat, these results provide convincing evidence of the importance of narrowly tuned afferents in the discrimination between sodium and nonsodium salts and suggest that this is a general coding principle in the gustatory system.
GDNF Selectively Protects Dopamine Neurons over Serotonin Neurons Against the Neurotoxic Effects of Methamphetamine
Authors: Cass Wayne A.
Published: April 2018

Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) and serotonin (5-HT) levels. Glial cell line-derived neurotrophic factor (GDNF) has pronounced effects on dopaminergic systemsin vivo, including partial neuroprotective effects against 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -induced lesions. The present study examined the ability of GDNF to prevent METH-induced reductions in potassium-evoked overflow of DA, and DA and 5-HT content, in striatum. GDNF (10 μg) or vehicle was injected into the right striatum of anesthetized rats. Twenty-four hours later, the rats were injected four times at 2 hr intervals with METH (5 mg/kg, s.c.) or saline. One week later,in vivoelectrochemistry was used to monitor the overflow of DA evoked by local potassium application. Evoked overflow of DA was dramatically decreased in the striatum of METH-treated animals. GDNF prevented the reduction in evoked overflow of DA in the right striatum of the METH-treated animals. After each experiment, the animals were killed, and striatal DA and 5-HT levels determined by HPLC. The METH treatment produced significant decreases in both neurotransmitters. GDNF administration prevented the reduction in striatal DA levels on the treated side of the brain, whereas levels on the contralateral side were still decreased. In dose–response studies, 1 μg of GDNF was as protective as 10 μg, whereas 0.1 μg was only partially protective. In contrast, 5-HT levels were only minimally protected by previous administration of GDNF. These results suggest that GDNF can selectively protect DA neurons, compared with 5-HT neurons, against the neurotoxic effects of METH.
Spontaneous Discharge and Peripherally Evoked Orofacial Responses of Trigemino–Thalamic Tract Neurons during Wakefulness and Sleep
Authors: Cairns Brian E. , McErlane Shelly A. , Fragoso Miguel C. , Jia William G. , Soja Peter J.
Published: April 2018

In the present study, ongoing and evoked activity of antidromically identified trigemino–thalamic tract (TGT) neurons was examined over the sleep–wake cycle in cats. There was no difference in the mean spike discharge rate of TGT neurons when quiet sleep (QS) and active sleep (AS) were compared with wakefulness (W). However, tooth pulp-evoked responses of TGT neurons were decreased during AS when compared to W. Conversely, the responses of TGT neurons to air puff activation of facial hair mechanoreceptors reciprocally increased during AS when compared to W. The present data demonstrate that ascending sensory information emanating from distinct orofacial areas is differentially modified during the behavioral state of AS. Specifically, the results obtained suggest that during AS, sensory information arising from hair mechanoreceptors is enhanced, whereas information arising from tooth pulp afferents is suppressed. These data may provide functional evidence for an AS-related gate control mechanism of sensory outflow to higher brain centers.
The Hypothalamic Ventromedial Nuclei Couple Activity in the Hypothalamo–Pituitary–Adrenal Axis to the Morning Fed or Fasted State
Authors: Choi SuJean , Horsley Cydney , Aguila Shirley , Dallman Mary F.
Published: April 2018

Function in the adrenocortical system is markedly altered by availability of food. Basal activity is lowest and stress responsivity highest in the morning when nocturnal rats eat ∼90% of their daily calories during the dark. After an overnight fast, basal corticotrophin and corticosteroid levels are elevated, and responsivity to stressors is decreased. Central neural sites that control these changes are unidentified. The hypothalamic ventromedial nuclei (VMN) appear to signal satiety; lesions result in increased food intake, obesity, and elevated basal insulin and corticosteroids. Thus, the VMN are good candidates for calorically mediated control of adrenocortical system function in satiated rats. We injected colchicine into the VMN to cause reversible inhibition of activity (Avrith and Mogenson, 1978) and tested the effects on basal and stimulated function in the adrenocortical system. Colchicine-injected rats that fedad libitumexhibited increased basal but reduced corticotrophin and corticosterone responses to restraint in the morning compared with controls. By contrast, after an overnight fast, control rats had increased basal adrenocortical hormones and decreased stress responses that did not differ from colchicine-injected rats. Colchicine was visualized within cells in the VMN for up to 5 d using fluorescein/colchicine, and the treatment did not cause increased gliosis; moreover, the functional effects of the injections were reversed within 15 d. We conclude that (1) the VMN serve to couple activity in the adrenocortical system to energy intake and (2) discrete colchicine injections provide a behaviorally and neuroendocrinologically useful period of inhibition without causing permanent functional damage.
Ultrastructural Localization Suggests that Retinal and Cortical Inputs Access Different Metabotropic Glutamate Receptors in the Lateral Geniculate Nucleus
Authors: Godwin Dwayne W. , Van Horn Susan C. , Erişir Alev , Sesma Michael , Romano Carmelo , Sherman S. Murray
Published: April 2018

Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)−1-amino-1,3-cyclopentanedicarboxylic acid produces a membrane depolarization that inactivates the low-threshold Ca2+spike, causing a transition from burst to tonic response mode. The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway. Two mGluRs, mGluR1α (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigeniculate nucleus. We also examined the ultrastructural localization of immunolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA. Label for the antibody directed against mGluR1α was primarily localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce. Label for the antibody directed against mGluR5 label was prominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide-linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.
5HT1BReceptor Agonists Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression of the Immediate–Early Genec-fosin the Suprachiasmatic Nucleus
Authors: Pickard Gary E. , Weber E. Todd , Scott Paul A. , Riberdy Anne F. , Rea Michael A.
Published: April 2018

The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT1Breceptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input.

The 5HT1Breceptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT1Areceptor antagonist (+)WAY 100135 or by the 5HT2receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mm) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT1Breceptors as determined using [125I]-iodocyanopindolol to define 5HT1Bbinding sites. These results are consistent with the interpretation that 5HT1Breceptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT1Bagonists inhibits retinohypothalamic input.
Activation of the CED3/ICE-Related Protease CPP32 in Cerebellar Granule Neurons Undergoing Apoptosis But Not Necrosis
Authors: Armstrong Robert C. , Aja Teresa J. , Hoang Kim D. , Gaur Smita , Bai Xu , Alnemri Emad S. , Litwack Gerald , Karanewsky Donald S. , Fritz Lawrence C. , Tomaselli Kevin J.
Published: April 2018

Neuronal apoptosis occurs during nervous system development and after pathological insults to the adult nervous system. Inhibition of CED3/ICE-related proteases has been shown to inhibit neuronal apoptosisin vitroandin vivo, indicating a role for these cysteine proteases in neuronal apoptosis. We have studied the activation of the CED3/ICE-related protease CPP32 in twoin vitromodels of mouse cerebellar granule neuronal cell death: K+/serum deprivation-induced apoptosis and glutamate-induced necrosis. Pretreatment of granule neurons with a selective, irreversible inhibitor of CED3/ICE family proteases, ZVAD-fluoromethylketone, specifically inhibited granule neuron apoptosis but not necrosis, indicating a selective role for CED3/ICE proteases in granule neuron apoptosis. Extracts prepared from apoptotic, but not necrotic, granule neurons contained a protease activity that cleaved the CPP32 substrate Ac-DEVD-aminomethylcoumarin. Induction of the protease activity was prevented by inhibitors of RNA or protein synthesis or by the CED3/ICE protease inhibitor. Affinity labeling of the protease activity with an irreversible CED3/ICE protease inhibitor, ZVK(biotin)D-fluoromethylketone, identified two putative protease subunits, p20 and p18, that were present in apoptotic but not necrotic granule neuron extracts. Western blotting with antibodies to the C terminus of the large subunit of mouse CPP32 (anti-CPP32) identified p20 and p18 as processed subunits of the CPP32 proenzyme. Anti-CPP32 specifically inhibited the DEVD-amc cleaving activity, verifying the presence of active CPP32 protease in the apoptotic granule neuron extracts. Western blotting demonstrated that the CPP32 proenzyme was expressed in granule neurons before induction of apoptosis. These results demonstrate that the CED3/ICE homolog CPP32 is processed and activated during cerebellar granule neuron apoptosis. CPP32 activation requires macromolecular synthesis and CED3/ICE protease activity. The lack of CPP32 activation during granule neuron necrosis suggests that proteolytic processing and activation of CED3/ICE proteases are specific biochemical markers of apoptosis.
Role of Ca2+Ions in Nicotinic Facilitation of GABA Release in Mouse Thalamus
Authors: Léna Clément , Changeux Jean-Pierre
Published: April 2018

Presynaptic nicotinic acetylcholine receptors (nAChRs) are present in many regions of the brain and potentially serve as targets for the pharmacological action of nicotinein vivo. To investigate their mechanism of action, we performed patch-clamp recordings in relay neurons from slices of thalamus sensory nuclei. In these nuclei, nAChR activation facilitated the release of the inhibitory neurotransmitter GABA. Micromolar concentrations of nicotinic agonists increased the frequency of miniature GABAergic synaptic currents and decreased the failure rate of evoked synaptic currents. These actions of nicotinic agonists were not observed in knock-out mice lacking the β2 nAChR subunit gene. Nicotinic effects were dependent on extracellular calcium ions, and they persisted when calcium was replaced by strontium or barium but not by magnesium. Furthermore, in high extracellular calcium concentrations, nicotinic agonists evoked an increase in spontaneous release lasting for minutes after removal of the agonist. This supports the view that presynaptic nAChRs facilitate the release of neurotransmitter by increasing the calcium concentrations in presynaptic nerve endings. With use of cadmium and nickel ions as selective blockers, it was found that in different sensory nuclei the presynaptic influx of calcium could result either from the activation of voltage-dependent calcium channels or from a direct influx through nAChR channels. Finally, we propose that the nicotinic facilitation of GABAergic transmission may contribute to the increase of signal-to-noise ratio observed in the thalamusin vivoduring arousal.
Mechanisms of C5a and C3a Complement Fragment-Induced [Ca2+]iSignaling in Mouse Microglia
Authors: Möller Thomas , Nolte Christiane , Burger Reinhard , Verkhratsky Alexej , Kettenmann Helmut
Published: April 2018

Microglial cells are activated in response to brain insults; the mechanisms of this process are not yet understood. One of the important signaling mechanisms that might be involved in microglia activation is related to changes in the intracellular calcium concentration ([Ca2+]i). Using fluo-3 microfluorimetry, we have found that external application of the complement fragment C5a (4–10 nm) induced [Ca2+]ielevation in microglial cellsin situin corpus callosum slices. Similarly, application of complement fragments C5a (0.1–10.0 nm) or C3a (100 nm) generates biphasic [Ca2+]itransients composed of an initial peak followed by a plateau in cultured microglia. Incubation of microglial cells for 30 min with pertussis toxin (PTX; 1 μg/ml) inhibited both C5a- and C3a-triggered [Ca2+]iresponses, suggesting the involvement of PTX-sensitive G-proteins in the signal transduction chain. Removal of Ca2+ions from the extracellular solution eliminated the plateau phase and limited the response to the initial peak. The restoration of the extracellular Ca2+concentration within 30–60 sec after the beginning of the complement fragment-induced [Ca2+]ielevation led to the recovery of the plateau phase. Inhibition of the endoplasmic reticulum Ca2+pumps with 500 nmthapsigargin transiently increased the [Ca2+]iand blocked the [Ca2+]isignals in response to subsequent complement fragment application. Our data suggest that complement factors induce [Ca2+]iresponses by Ca2+release from internal pools and subsequent activation of Ca2+entry controlled by the filling state of the intracellular Ca2+depots.
Resetting the Biological Clock: Mediation of Nocturnal CREB Phosphorylation via Light, Glutamate, and Nitric Oxide
Authors: Ding Jian M. , Faiman Lia E. , Hurst William J. , Kuriashkina Liana R. , Gillette Martha U.
Published: April 2018

Synchronization between the environmental lighting cycle and the biological clock in the suprachiasmatic nucleus (SCN) is correlated with phosphorylation of the Ca2+/cAMP response element binding protein (CREB) at the transcriptional activating site Ser133. Mechanisms mediating the formation of phospho-CREB (P-CREB) and their relation to clock resetting are unknown. To address these issues, we probed the signaling pathway between light and P-CREB. Nocturnal light rapidly and transiently induced P-CREB-like immunoreactivity (P-CREB-lir) in the rat SCN. Glutamate (Glu) or nitric oxide (NO) donor administrationin vitroalso induced P-CREB-lir in SCN neurons only during subjective night. Clock-controlled sensitivity to phase resetting by light, Glu, and NO is similarly restricted to subjective night. The effects of NMDA and nitric oxide synthase (NOS) antagonists on Glu-mediated induction of P-CREB-lir paralleled their inhibition of phase shifting. Significantly, among neurons in which P-CREB-lir was induced by light were NADPH-diaphorase-positive neurons of the SCN’s retinorecipient area. Glu treatment increased the intensity of a 43 kDa band recognized by anti-P-CREB antibodies in subjective night but not day, whereas anti-αCREB-lir of this band remained constant between night and day. Inhibition of NOS during Glu stimulation diminished the anti-P-CREB-lir of this 43 kDa band. Together, these data couple nocturnal light, Glu, NMDA receptor activation and NO signaling to CREB phosphorylation in the transduction of brief environmental light stimulation of the retina into molecular changes in the SCN resulting in phase resetting of the biological clock.
Temporal and Spatial Expression Patterns of Transgenes Containing Increasing Amounts of theDrosophilaClock Geneperiodand alacZReporter: Mapping Elements of the PER Protein Involved in Circadian Cycling
Authors: Stanewsky Ralf , Frisch Brigitte , Brandes Christian , Hamblen-Coyle Melanie J. , Rosbash Michael , Hall Jeffrey C.
Published: April 2018

Rhythmic oscillations of the PER protein, the product of theDrosophila period(per) gene, in brain neurons of the adult fly are strongly involved in the control of circadian rhythms. We analyzed temporal and spatial expression patterns of threeper–reporterfusion genes, which share the same 4 kb regulatory upstream region but contain increasing amounts ofper’s coding region fused in frame to the bacteriallacZgene. The fusion proteins contained either the N-terminal half (SG), the N-terminal two-thirds (BG), or nearly all (XLG) of the PER protein. All constructs led to reporter signals only in the knownper-expressing cell types within the anterior CNS and PNS. Whereas the staining intensity of SG flies was constantly high at different Zeitgeber times, thein situsignals in BG and XLG flies cycled with ∼24 hr periodicity in the PER-expressing brain cells in wild-type andper01loss of function flies. Despite the rhythmic fusion-gene expression within the relevant neurons ofper01BG flies, their locomotor activity in light/dark cycling conditions and in constant darkness was identical to that ofper01controls, uncoupling protein cycling from rhythmic behavior. The XLG construct restored weak behavioral rhythmicity to (otherwise)per01flies, indicating that the C-terminal third of PER (missing in BG) is necessary to fulfill the biological function of this clock protein.
Neuronal Adaptations to Changes in the Social Dominance Status of Crayfish
Authors: Yeh Shih-Rung , Musolf Barbara E. , Edwards Donald H.
Published: April 2018

The effect of superfused serotonin (5-HT; 50 μm) on the synaptic responses of the lateral giant (LG) interneuron in crayfish was found to depend on the social status of the animal. In socially isolated animals, 5-HT persistently increased the response of LG to sensory nerve shock. After social isolates were paired in a small cage, they fought and determined their dominant and subordinate status. After 12 d of pairing, 5-HT reversibly inhibited the response of LG in the social subordinate and reversibly increased the response of LG in the social dominant crayfish. The effect of 5-HT changed approximately linearly from response enhancement to inhibition in the new subordinate over the 12 d of pairing. If, after 12 d pairing, the subordinate was reisolated for 8 d, the response enhancement was restored. If the subordinate, instead, was paired with another subordinate and became dominant in this new pair, the inhibitory effect of 5-HT changed to an enhancing effect over the next 12 d of pairing. If, however, two dominant crayfish were paired and one became subordinate, the enhancing effect of 5-HT persisted in the new subordinate even after 38 d pairing. These different effects of serotonin result from the action of two or more molecular receptors for serotonin. A vertebrate 5-HT1agonist had no effect on social isolates but reversibly inhibited the response of LG in both dominant and subordinate crayfish. The inhibitory effects of the agonist developed approximately linearly over the first 12 d of pairing. A vertebrate 5-HT2agonist persistently increased the response of LG in isolate crayfish and reversibly increased the response of the cell in dominant and subordinate crayfish. Finally, although neurons that might mediate these effects of superfused 5-HT are unknown, one pair of 5-HT-immunoreactive neurons appears to contact the LG axon and initial axon segment in each abdominal ganglion in its projection caudally from the thorax.
Altered Excitability of the Crayfish Lateral Giant Escape Reflex during Agonistic Encounters
Authors: Krasne Franklin B. , Shamsian Ashkan , Kulkarni Raghavendra
Published: April 2018

The excitability of the lateral giant escape reflex of socially dominant and submissive crayfish at rest and during agonistic encounters was studied and compared. During agonistic encounters the excitability of the lateral giant reflex falls, substantially in subordinates and slightly in dominants, whereas at rest excitability seems to be independent of social status. Thus, paradoxically, socially dominant animals are more likely to execute lateral giant escape reactions during interactions than are subordinates. It is suggested that subordinates under threat of attack tend to engage circuitry involved in flexible, nonreflex (“voluntary”) types of escape not mediated by giant neurons and therefore inhibit giant neuron-mediated reflex circuitry that produces prompt, but less adaptive, responses. In contrast, dominants go about their business, mainly ignoring their conspecifics and relying on reflex escape to protect them from unexpected attack. Consistent with this view, escape of subordinates during agonistic encounters is mediated by nongiant, not reflex, circuitry. These observations and their interpretation suggest a possible functional role for recently described social status-dependent serotonergic modulation of the lateral giant reflex, which is inhibitory in sign in subordinates and facilitatory in dominants.
A Developmental Gene (Tolloid/BMP-1) Is Regulated inAplysiaNeurons by Treatments that Induce Long-Term Sensitization
Authors: Liu Qing-R , Hattar Samer , Endo Shogo , MacPhee Kathleen , Zhang Han , Cleary Leonard J. , Byrne John H. , Eskin Arnold
Published: April 2018

Long-term sensitization training, or procedures that mimic the training, produces long-term facilitation of sensory-motor neuron synapses inAplysia. The long-term effects of these procedures require mRNA and protein synthesis (Montarolo et al., 1986;Castellucci et al., 1989). Using the techniques of differential display reverse transcription PCR (DDRT-PCR) and ribonuclease protection assays (RPA), we identified a cDNA whose mRNA level was increased significantly in sensory neurons by treatments of isolated pleural-pedal ganglia with serotonin for 1.5 hr or by long-term behavioral training ofAplysia. The effects of serotonin and behavioral training on this mRNA were mimicked by treatments that elevate cAMP. TheAplysiamRNA increased by serotonin and behavioral training was 41–45% identical to a developmentally regulated gene family which includesDrosophila tolloidand human bone morphogenetic protein-1 (BMP-1). Bothtolloidand BMP-1 encode metalloproteases that might activate TGF-β (transforming growth factor β)-like molecules or process procollagens.Aplysia tolloid/BMP-1-like protein (apTBL-1) might regulate the morphology and efficacy of synaptic connections between sensory and motor neurons, which are associated with long-term sensitization.
Detection and Discrimination of First- and Second-Order Motion in Patients with Unilateral Brain Damage
Authors: Greenlee Mark W. , Smith Andy T.
Published: April 2018

The present investigation explored the extent to which extrastriate cortex is necessary for various aspects of motion processing and whether the processing of first-order (Fourier) and second-order (non-Fourier) motion involves the same extrastriate cortical regions. Orientation, direction, and speed discrimination thresholds were measured in 21 patients with unilateral damage to the lateral occipital, temporal, or posterior parietal cortex. Their results were compared with those of 14 age-matched control subjects. The stimuli were static random-dot noise patterns, the luminance of which (first-order) or contrast (second-order) was modulated by a drifting sinusoid. Each image was presented at an eccentricity of 5.6 deg in one of the four visual quadrants. The contrasts required to identify orientation and direction were measured in a forced-choice paradigm for three speeds (1.5, 3, and 6 deg/sec). Speed discrimination performance was measured for stimuli presented simultaneously in two of the four quadrants. The results indicate the following: (1) orientation thresholds were increased only slightly in the patients; (2) direction thresholds were modestly elevated, and this effect was more pronounced for second-order stimuli than for first-order stimuli; (3) speed discrimination thresholds were elevated significantly in the patients with lesions in the region bordering superior-temporal and lateral-occipital cortex; and (4) speed discrimination thresholds for first-order stimuli were more elevated than those for second-order stimuli. The results suggest that there is substantial overlap in the cortical areas involved in first- and second-order speed discrimination.
Differential Influence of Associative and Nonassociative Learning Mechanisms on the Responsiveness of Prefrontal and Accumbal Dopamine Transmission to Food Stimuli in Rats FedAd Libitum
Authors: Bassareo Valentina , Di Chiara Gaetano
Published: April 2018

Feeding a novel food (Fonzies) to rats fedad libitumwith standard food increased extracellular dopamine (DA) in the medial prefrontal cortex (PFCX) and in the medial nucleus accumbens (NAc). Previous Fonzies feeding, although it did not affect the increase of extracellular DA in the PFCX in response to Fonzies feeding, blunted that increase in the NAc (habituation); recovery from habituation in the NAc was complete 5 d after previous Fonzies feeding. Predictive association of an otherwise neutral stimulus extrinsic to Fonzies (empty plastic box) with Fonzies feeding resulted in the acquisition by the stimulus of the property to elicit incentive responses directed toward the stimulus and to increase extracellular DA in the PFCX. However, the same stimulus, or a more complex stimulus including intrinsic stimuli (Fonzies-filled plastic box), failed to acquire the ability to modify extracellular DA in the NAc. Pseudoconditioning, i.e., nonpredictive association of the extrinsic stimulus (empty box) with Fonzies feeding, did not result in acquisition by the stimulus of the property to elicit incentive responses and to increase extracellular DA in the PFCX. Repeated nonreinforced presentation of previously conditioned extrinsic stimuli (empty box) resulted in extinction of the property to elicit incentive responses and to increase extracellular DA in the PFCX. These results indicate that in rats fedad libitum, phasic activation of mesocortical and mesolimbic DA systems by motivational stimuli is differentially influenced by associative (conditioning) and nonassociative (habituation) learning mechanisms and is differentially related to acquisition and expression of incentive motivation.
Formation of Oligomers Containing the β3 and β4 Subunits of the Rat Nicotinic Receptor
Authors: Forsayeth John R. , Kobrin Eugenia
Published: April 2018

The role of the β3 and β4 subunits of the nicotinic acetylcholine receptor in brain is still unclear. We investigated nicotinic receptor structure with antibodies directed against unique regions of the β3 and β4 subunits of the rat nicotinic acetylcholine receptor. Anti-β4 detected a single band of 66 kDa in most regions of the brain that was strongest in striatum and cerebellum. The 60 kDa β3 subunit was detected primarily in striatum and cerebellum, and faintly in hippocampus. Immunoprecipitation experiments established that the two subunits were coassembled in the cerebellum along with the β2 subunit. Antibodies against the α4, β2, β3, and β4 subunits immunoprecipitated ∼75% of the bungarotoxin-insensitive nicotinic receptor from cerebellar extracts as determined by nicotine-dependent acetylcholine binding. Transfection of COS cells with cDNAs for these four subunits induced expression of a high affinity nicotinic receptor. Omission of only a single subunit from the transfection affected either theBmaxor the apparentKDof the receptor. Our data suggest that the β3 subunit functions as a structural entity that links a relatively unstable α4β2 heterodimer to a more stable α4β4 heterodimer. The agonist-binding site formed by α4β2 has a much greater affinity than does that formed by α4β4. In this respect, nicotinic receptors that contain the β3 subunit are structurally homologous to the muscle nicotinic receptor.
Insulin-Like Growth Factor and Potassium Depolarization Maintain Neuronal Survival by Distinct Pathways: Possible Involvement of PI 3-Kinase in IGF-1 Signaling
Authors: D’Mello Santosh R. , Borodezt Kristin , Soltoff Stephen P.
Published: April 2018

Cultured cerebellar granule neurons die by apoptosis when switched from a medium containing an elevated level of potassium (K+) to one with lower K+(5 mm). Death resulting from the lowering of K+can be prevented by insulin-like growth factor (IGF-1). To understand how IGF-1 inhibits apoptosis and maintains neuronal survival, we examined the role of phosphoinositide 3-kinase (PI 3-kinase). Activation of PI 3-kinase has been shown previously to be required for NGF-mediated survival in the PC12 pheochromocytoma cell line. We find that in primary neurons, IGF-1 treatment leads to a robust activation of PI 3-kinase, as judged by lipid kinase assays and Western blot analysis. Activation of PI 3-kinase is likely to occur via tyrosine phosphorylation of the insulin receptor substrate protein. Treatment with two chemically distinct inhibitors of PI 3-kinase, wortmannin and LY294002, reduces PI 3-kinase activation by IGF-1 and inhibits its survival-promoting activity, suggesting that PI 3-kinase is necessary for IGF-1-mediated survival. Death resulting from PI 3-kinase blockade is accompanied by DNA fragmentation, a hallmark of apoptosis. Furthermore, neurons subjected to PI 3-kinase blockade can be rescued by transcriptional and translation inhibitors, suggesting that IGF-1-mediated activation of PI 3-kinase leads to a suppression of “killer gene” expression. In sharp contrast to IGF-1, elevated K+does not activate PI 3-kinase and can maintain neuronal survival in the presence of PI 3-kinase inhibitors. Therefore, survival of granule neurons can be maintained by PI 3-kinase dependent (IGF-1-activated) and independent (elevated K+-activated) pathways.
Cloning and Expression of a Rat Brain Interleukin-1β-Converting Enzyme (ICE)-Related Protease (IRP) and Its Possible Role in Apoptosis of Cultured Cerebellar Granule Neurons
Authors: Ni Binhui , Wu Xin , Du Yansheng , Su Yuan , Hamilton-Byrd Elizabeth , Rockey Pamela K. , Rosteck Jr. Paul , Poirier Guy G. , Paul Steven M.
Published: April 2018

Several members of the IL-1β-converting enzyme (ICE) family of proteases recently have been implicated in the intracellular cascade mediating the apoptotic death of various cell types. It is unclear, however, whether ICE-related proteases are involved in apoptosis of mammalian neurons and, if so, how they are activated. Here we report the cloning of an ICE-related protease (IRP) from rat brain, which displays strong sequence identity to human CPP32.In situhybridization histochemistry reveals that this IRP mRNA is expressed in neuron-enriched regions of the developing and adult rat brain but is profoundly downregulated in the adult (compared with developing) brain. To investigate whether this IRP is involved in the death of neurons in the developing brain, we studied IRP expression in cultured cerebellar granule neurons. In cultured cerebellar granule neurons, reduction of extracellular K+reliably induces apoptosis and stimulates overexpression of IRP mRNA. The latter is especially prominent 4 hr after switching from high K+to low K+medium. The expression of IRP mRNA was maintained at this level for at least 8 hr and was followed by apoptotic death of these neurons. Induction of IRP mRNA and cell death are blocked completely by adding depolarizing concentrations of K+≤90 min after switching to low K+medium (i.e., before the commitment point for apoptosis) and partially blocked by brain-derived neurotrophic factor (BDNF), which also partially rescues granule neurons from low K+-induced apoptosis. In addition, overexpression of IRP cDNA in HeLa cells results in cell death accompanied by strong internucleosomal cleavage of DNA, a typical feature of apoptosis. Finally, we detected cleavage of the putative death substrate poly (ADP-ribose) polymerase (PARP), beginning 8 hr after changing from high K+to low K+medium, coinciding with the time course of induced expression of the IRP gene. Our data suggest that transcriptional activation of IRP could be one of the mechanisms involved in the apoptotic death of cerebellar granule neurons.
Combinations of AMPA Receptor Subunit Expression in Individual Cortical Neurons Correlate with Expression of Specific Calcium-Binding Proteins
Authors: Kondo Masahiro , Sumino Rhyuji , Okado Haruo
Published: April 2018

The functional properties of AMPA-type glutamate receptors are determined by their subunit composition. We detected the expression of the AMPA receptor subunits (GluR1–GluR4) in neurons in the somatosensory cortex of adult rats by combining nonradioactivein situhybridization using digoxigenin-labeled RNA probes of GluR1 and GluR2 with immunocytochemistry using specific antibodies against GluR1, GluR2/3, and GluR4. On the basis of differential expression of the GluR1 and GluR2 subunits, we classified the cortical neurons into four categories. To correlate the differential expression of AMPA receptor subunits in each neuron with that of two calcium-binding proteins, parvalbumin and calbindin-D28k, we used a triple-labeling method. The majority of cortical neurons (∼2/3) showed expression of GluR2 and undetectable expression of GluR1. GluR1-/GluR2-expressing neurons and GluR1-expressing/GluR2-undetectable neurons comprised ∼1/10 each. Regarding the morphology, most GluR1-undetectable/GluR2-expressing neurons were pyramidal cells in layers II/III, V, and VI, whereas most GluR1-expressing/GluR2-undetectable neurons were nonpyramidal cells in layers II–VI. The GluR1-/GluR2-expressing neurons were either pyramidal or nonpyramidal. The majority of GluR1-/GluR2-expressing nonpyramidal cells was intensely stained with monoclonal antibody against calbindin-D28k, and one-half of the GluR1-undetectable/GluR2-expressing pyramidal neurons in layer II/III were lightly stained with this antibody. Most of GluR1-expressing/GluR2-undetectable neurons possessed parvalbumin immunoreactivity. These results indicate that neurons in the rat somatosensory cortex express differential combinations of GluR subunits, which correlate with the specific expression of the calcium-binding proteins.
Identification of a Vesicular Pool of Calcium Channels in the Bag Cell Neurons ofAplysia californica
Authors: White Benjamin H. , Kaczmarek Leonard K.
Published: April 2018

To study the molecular mechanism of calcium current modulation in the bag cell neurons ofAplysia californica, we have identified calcium channel subtypes expressed in these cells and analyzed their distribution using channel-specific antibodies. Using PCR to amplify reverse-transcribed RNA from bag cell clusters, we identified two classes of calcium channel α1subunit. One, BCCa-I, belongs to the ABE subfamily of calcium channels, whereas the other, BCCa-II, belongs to the SCD subfamily. Antibodies generated against the bag cell calcium channels recognize membrane proteins of ∼210 and 280 kDa on immunoblots. Both channels are expressed in the bag cell clusters as well as in other parts of theAplysianervous system. BCCa-II also localizes to glia and muscle. The subcellular distribution of the two channel types is strikingly different. Antibody staining of bag cell neurons in primary culture shows that BCCa-II is present on the plasma membrane, whereas BCCa-I has a punctate, intracellular distribution consistent with a vesicular localization. The BCCa-I-containing vesicles are found in bag cell neuron somata and growth cones and occasionally in neuritic hotspots. Their distribution is similar but not identical to that of LysoTracker Red, a marker for acidic organelles, but unlike that of dense-core vesicles containing egg-laying hormone. The vesicular channels may represent the protein kinase C-sensitive calcium channels of bag cell neurons that are believed to enhance hormonal release during electrical activity.
d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors
Authors: Schell Michael J. , Brady Jr. Roscoe O. , Molliver Mark E. , Snyder Solomon H.
Published: April 2018

d-Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting thatd-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immunohistochemical localizations ofd-serine, glycine, and NMDA receptors in rat brain. In the telencephalon,d-serine is concentrated in protoplasmic astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ultrastructural examination of the CA1 region of hippocampus revealsd-serine in the cytosolic matrix of astrocytes that ensheath neurons and blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast, glycine immunoreactivity in telencephalon is the lowest in brain. During postnatal week 2,d-serine levels in cerebellum are comparable to those in adult cerebral cortex but fall to undetectable levels by day 26. During week 2, we observe parallel ontogeny ofd-serine in Bergmann glia and NR2A/B in Purkinje cells, suggesting a role for astrocyticd-serine in NMDA receptor-mediated synaptogenesis.d-Serine in the radial processes of Bergmann glia is also well positioned to regulate NMDA receptor-dependent granule cell migration. In the inner granule layer,d-serine is found transiently in protoplasmic astrocytes surrounding glomeruli, where it could regulate development of the mossy fiber/granule cell synapse.d-Serine seems to be the endogenous ligand of glycine sites in the telencephalon and developing cerebellum, whereas glycine predominates in the adult cerebellum, olfactory bulb, and hindbrain.
Coexpression of Two Odorant-Binding Protein Homologs inDrosophila: Implications for Olfactory Coding
Authors: Hekmat-Scafe Daria S. , Steinbrecht R. Alexander , Carlson John R.
Published: April 2018

Odorant-binding proteins (OBPs) are small soluble proteins present in the aqueous medium surrounding olfactory receptor neurons. Their function in olfaction is still unknown: they have been proposed to facilitate the transit of hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to play a role in chemosensory coding. In this study we examine the genomic organization and expression patterns of twoolfactory-specific genes (OS-EandOS-F) ofDrosophila melanogaster, the products of which are members of a protein family inDrosophilasharing sequence similarity with moth OBPs. We show that theOS-EandOS-Ftranscription units are located <1 kb apart. They are oriented in the same direction and display a similar intron–exon organization. Expression of both OS-E and OS-F proteins is restricted spatially to the ventrolateral region of theDrosophilaantenna. Within this region both OS-E and OS-F proteins are expressed within two different types of sensory hairs: in most, if not all, sensilla trichodea and in ∼40% of the interspersed small sensilla basiconica. We consistently observe that OS-E and OS-F are coexpressed, indicating that an individual sensillum can contain more than one odorant-binding protein. The functional significance of the observed expression pattern and its implications for olfactory coding are discussed.
Facilitation of N-Type Calcium Current Is Dependent on the Frequency of Action Potential-Like Depolarizations in Dissociated Cholinergic Basal Forebrain Neurons of the Guinea Pig
Authors: Williams Sylvain , Serafin Mauro , Mühlethaler Michel , Bernheim Laurent
Published: April 2018

Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by G-proteins can be transiently relieved (facilitated) by strong depolarizing prepulses. However, with respect to the physiological significance of facilitation, it remains to be established if it can be induced by action potentials (AP) in central neurons. With the use of whole-cell recordings of dissociated cholinergic basal forebrain neurons of the guinea pig, it is shown that the GTPγS-inhibited HVA currents that occur throughN-ethylmaleimide (NEM)-sensitive Gi–Gosubtypes of G-proteins can be facilitated. Furthermore, although different types of HVA channels are present in these neurons, facilitation occurred mostly through disinhibition of the N-type current. On the basis of data indicating that the recovery from facilitation was relatively slow, we tested if more physiological stimuli that crudely mimicked APs (2 msec long depolarizations to 40 mV from a holding of −50 mV) potentially could induce facilitation of HVA currents inhibited by GTPγS and cholinergic agonists. Indeed, evidence is provided that the extent of facilitation is dependent on both the number and frequency of AP-like depolarizations. These results suggest that firing rates and patterns of discharge of neurons could influence their responsiveness to transmitters acting on N-type HVA calcium channels.