bluuebunny/crossref_metadata_2025 huggingface dataset:
α2-Adrenoceptor-Mediated Presynaptic Modulation of GABAergic Transmission in Mechanically Dissociated Rat Ventrolateral Preoptic Neurons
Authors: Matsuo Shin-ichiro , Jang Il-Sung , Nabekura Junichi , Akaike Norio
Published: May 2006

The ventrolateral preoptic nucleus (VLPO) is a key nucleus involved in the homeostatic regulation of sleep-wakefulness. Little is known, however, about the cellular mechanisms underlying its role in sleep regulation and how the neurotransmitters, such as GABA and noradrenaline (NA), are involved. In the present study we investigated GABAergic transmission to acutely dissociated VLPO neurons using an enzyme-free, mechanical dissociation procedure in which functional terminals remained adherent and we investigated how this GABAergic transmission was modulated by NA. As previously reported in slices, NA hyperpolarized multipolar VLPO neurons and depolarized bipolar VLPO neurons. NA also inhibited the release of GABA onto multipolar VLPO neurons but had no effect on GABAergic transmission to bipolar neurons. The inhibition of release was mediated by presynaptic α2adrenoceptors coupled to N-ethylmaleimide (NEM)-sensitive G-proteins which appeared to act via inhibition of adenylate cyclase and subsequent decreases in protein kinase A activity. The inhibition of GABA release did not, however, involve an inhibition of external Ca2+influx. The results indicate that all VLPO neurons contain GABAergic inputs and that the different morphological subgroups of VLPO neurons are correlated not only to different postsynaptic responses to NA but also to different presynaptic NA responses. Furthermore our results demonstrate an additional mechanism by which NA can modulate the excitability of multipolar VLPO neurons which may have important implications for its role in regulating sleep/wakefulness.
Heading Representation in MST: Sensory Interactions and Population Encoding
Authors: Page William K. , Duffy Charles J.
Published: May 2006

Dorsal medial superior temporal cortex (MSTd)'s population response encodes heading direction from optic flow seen during fixation or pursuit. Vestibular responses in these neurons might enhance heading representation during self-movement in light or provide an alternative basis for heading representation during self-movement in darkness. We have compared these hypotheses by recording MSTd neuronal responses to translational self-movement in light and darkness, during fixation and pursuit. Translational movement in darkness, with gaze fixed, evokes transient vestibular responses during acceleration that reverse directionality during deceleration and persist without a fixation target. Movement in light increases the amplitude and duration of these responses so they mimic responses to simulated optic flow presented without translational movement. Pursuit of a stationary landmark during translational movement combines vestibular and visual effects with pursuit responses. Vestibular, visual, and pursuit effects interact so that single neuron heading responses vary across the stimulus period and between stimulus conditions. Combining single neuron responses by population vector summation yields stronger heading estimates in light than in darkness, with gaze fixed or during landmark pursuit. Adding translational movement to robust optic flow stimuli does not augment the population response. Vestibular signals enhance single neuron responses in light and maintain population heading estimation in darkness, potentially extending MSTd's heading representation across the continuum of naturalistic self-movement conditions.
NPY Sensitivity and Postsynaptic Properties of Heterotopic Neurons in the MAM Model of Malformation-Associated Epilepsy
Authors: Pentney A. R. , Baraban S. C. , Colmers W. F.
Published: May 2006

Neuronal migration disorders (NMDs) can be associated with neurological dysfunction such as mental retardation, and clusters of disorganized cells (heterotopias) often act as seizure foci in medically intractable partial epilepsies. Methylazoxymethanol (MAM) treatment of pregnant rats results in neuronal heterotopias in offspring, especially in hippocampal area CA1. Although the neurons in dysplastic areas in this model are frequently hyperexcitable, the precise mechanisms controlling excitability remain unclear. Here, we used IR-DIC videomicroscopy and whole cell voltage-clamp techniques to test whether the potent anti-excitatory actions of neuropeptide Y (NPY) affected synaptic excitation of heterotopic neurons. We also compared several synaptic and intrinsic properties of heterotopic, layer 2–3 cortical, and CA1 pyramidal neurons, to further characterize heterotopic cells. NPY powerfully inhibited synaptic excitation onto normal and normotopic CA1 cells but was nearly ineffective on responses evoked in heterotopic cells from stimulation sites within the heterotopia. Glutamatergic synaptic responses on heterotopic cells exhibited a comparatively small, d-2-amino-5-phosphopentanoic acid-sensitive, N-methyl-d-aspartate component. Heterotopic neurons also differed from normal CA1 cells in postsynaptic membrane currents, possessing a prominent inwardly rectifying K+ current sensitive to Cs+and Ba2+, similar to neocortical layer 2–3 pyramidal cells. CA1 cells instead had a prominent Cs+- and 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride-sensitive I h and negligible inward rectification, unlike heterotopic cells. Thus heterotopic CA1 cells appear to share numerous physiological similarities with neocortical neurons. The lack of NPY's effects on intra-heterotopic inputs, the small contribution of I h, and abnormal glutamate receptor function, may all contribute to the lowered threshold for epileptiform activity observed in hippocampal heterotopias and could be important factors in epilepsies associated with NMDs.
Characterization of Neuronal Nicotinic Acetylcholine Receptors in the Membrane of Unmyelinated Human C-Fiber Axons by In Vitro Studies
Authors: Lang P. M. , Burgstahler R. , Sippel W. , Irnich D. , Schlotter-Weigel B. , Grafe P.
Published: May 2006

Application of acetylcholine to peripheral nerve terminals in the skin is a widely used test in studies of human small-fiber functions. However, a detailed pharmacological profile and the subunit composition of nicotinic acetylcholine receptors in human C-fiber axons are not known. In the present study, we recorded acetylcholine-induced changes of the excitability and of the intracellular Ca2+concentration in C-fiber axons of isolated human nerve segments. In addition, using immunohistochemistry, an antibody of a subtype of nicotinic acetylcholine receptor was tested. Acetylcholine and agonists reduced the current necessary for the generation of action potentials in C fibers by ≤30%. This increase in axonal excitability was accompanied by a rise in the free intracellular Ca2+concentration. The following rank order of potency for agonists was found: epibatidine >> 5-Iodo-A-85380 > 1,1-dimethyl-4-phenylpiperazinium iodide > nicotine > cytisine > acetylcholine; choline had no effect. The epibatidine-induced increase in axonal excitability was blocked by mecamylamine and, less efficiently, by methyllycacontine and dihydro-β-erythroidine. Many C-fiber axons were labeled by an antibody that recognizes the α5 subunit of nicotinic acetylcholine receptors. In summary, electrophysiological and immunohistochemical data indicate the functional expression of nicotinic acetylcholine receptors composed of α3, α5, and β4 but not of α4/β2 or of α7 subunits in the axonal membrane of unmyelinated human C fibers. In addition, the observations suggest that the axonal membrane of C fibers in isolated segments of human sural nerve can be used as a model for presumed cholinergic chemosensitivity of axonal terminals.
Adenosine A1Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in Immature Rat Hippocampal CA1 Neurons
Authors: Jeong Hyo-Jin , Jang Il-Sung , Nabekura Junichi , Akaike Norio
Published: May 2006

In the mechanically dissociated rat hippocampal CA1 neurons with native presynaptic nerve endings, namely “synaptic bouton” preparation, the purinergic modulation of spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) was investigated using whole-cell recording mode under the voltage-clamp conditions. In immature neurons, adenosine (10 μM) reversibly decreased GABAergic mIPSC frequency without affecting the mean current amplitude. The inhibitory effect of adenosine transmission was completely blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), a selective Α1receptor antagonist, and was mimicked by N6-cyclopentyladenosine (CPA, 1 μM), a selective Α1receptor agonist. However, CPA had no effect on GABAergic mIPSC frequency in postnatal 30 day neurons. N-ethylmaleimide (10 μM), a guanosine 5′-triphosphate binding protein uncoupler, and Ca2+-free external solution removed the CPA-induced inhibition of mIPSC frequency. K+channel blockers, 4-aminopyridine (100 μM) and Ba2+(1 mM), had no effect on the inhibitory effect of CPA on GABAergic mIPSC frequency. Stimulation of adenylyl cyclase with forskolin (10 μM) prevented the CPA action on GABAergic mIPSC frequency. Rp-cAMPS (100 μM), a selective PKA inhibitor, also blocked the CPA action. It was concluded that the activation of presynaptic Α1receptors modulates the probability of spontaneous GABA release via cAMP- and protein kinase A dependent pathway. This Α1receptor-mediated modulation of GABAergic transmission may play an important role in the regulation of excitability of immature hippocampal CA1 neurons.
Color Sensitivity of Cells Responsive to Complex Stimuli in the Temporal Cortex
Authors: Edwards Robin , Xiao Dengke , Keysers Christian , Földiák Peter , Perrett David
Published: May 2006

The inferotemporal (IT) cortex of the monkey lies at the head of the ventral visual pathway and is known to mediate object recognition and discrimination. It is often assumed that color plays a minor role in the recognition of objects and faces because discrimination remains highly accurate with black-and-white images. Furthermore it has been suggested that for rapid presentation and reaction tasks, object classification may be based on a first wave of feedforward visual information, which is coarse and achromatic. The fine detail and color information follows later, allowing similar stimuli to be discriminated. To allow these theories to be tested, this study investigates whether the presence of color affects the response of IT neurons to complex stimuli, such as faces, and whether color information is delayed with respect to information about stimulus form in these cells. Color, achromatic, and false-color versions of effective stimuli were presented using a rapid serial visual presentation paradigm, and responses recorded from single cells in IT of the adult monkey. Achromatic images were found to evoke significantly reduced responses compared with color images in the majority of neurons (70%) tested. Differential activity for achromatic and colored stimuli was evident from response onset with no evidence to support the hypothesis that information about object color is delayed with respect to object form. A negative correlation ( P < 0.01) was found between cell latency and color sensitivity, with the most color-sensitive cells tending to respond earliest. The results of this study suggest a strong role for color in familiar object recognition and provide no evidence to support the idea of a first wave of form processing in the ventral stream based on purely achromatic information.
GABAAReceptor Activation Modulates Corneal Unit Activity in Rostral and Caudal Portions of Trigeminal Subnucleus Caudalis
Authors: Hirata Harumitsu , Okamoto Keiichiro , Bereiter David A.
Published: May 2006

Corneal nociceptors terminate at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/upper cervical spinal cord (Vc/C1) junction regions of the lower brain stem. The aims of this study were to determine if local GABAAreceptor activation modifies corneal input to second-order neurons at these regions and if GABAAreceptor activation in one region affects corneal input to the other region. In barbiturate-anesthetized male rats, corneal nociceptors were excited by pulses of CO2gas, and GABAAreceptors were activated by microinjections of the selective agonist muscimol. Local muscimol injection at the site of recording inhibited all Vi/Vc and Vc/C1 units tested and was reversed partially by bicuculline. To test for ascending intersubnuclear communication, muscimol injection into the caudal Vc/C1 junction, remote from the recording site at the Vi/Vc transition, inhibited the evoked response of most corneal units, although some neurons were enhanced. Injection of the nonselective synaptic blocking agent, CoCl2, remotely into the Vc/C1 region inhibited the evoked response of all Vi/Vc units tested. To test for descending intersubnuclear communication, muscimol was injected remotely into the rostral Vi/Vc transition and enhanced the evoked activity of all corneal units tested at the caudal Vc/C1 junction. These results suggest that GABAAreceptor mechanisms play a significant role in corneal nociceptive processing by second-order trigeminal brain stem neurons. GABAAreceptor mechanisms act locally at both the Vi/Vc transition and Vc/C1 junction regions to inhibit corneal input and act through polysynaptic pathways to modify corneal input at multiple levels of the trigeminal brain stem complex.
Effect of Extracellular Calcium on Excitability of Guinea Pig Airway Vagal Afferent Nerves
Authors: Undem Bradley J. , Oh Eun Joo , Lancaster Eric , Weinreich Daniel
Published: May 2006

The effect of reducing extracellular calcium concentration ([Ca2+]o) on vagal afferent excitability was analyzed in a guinea pig isolated vagally innervated trachea-bronchus preparation. Afferent fibers were characterized as either having low-threshold, rapidly adapting mechanosensors (Aδ fibers) or nociceptive-like phenotypes (Aδ and C fibers). The nociceptors were derived from neurons within the jugular ganglia, whereas the low-threshold mechanosensors were derived from neurons within the nodose ganglia. Reducing [Ca2+]odid not affect the excitability of the low-threshold mechanosensors in the airway. By contrast, reducing [Ca2+]oselectively increased the excitability of airway nociceptors as manifested by a substantive increase in action potential discharge in response to mechanical stimulation, and in a subset of fibers, by overtly evoking action potential discharge. This increase in the excitability of nociceptors was not mimicked by a combination of ω-conotoxin and nifedipine or tetraethylammonium. Whole cell patch recordings from airway-labeled and unlabeled neurons in the vagal jugular ganglia support the hypothesis that [Ca2+]oinhibits a nonselective cation conductance in vagal nociceptors that may serve to regulate excitability of the nerve terminals within the airways.
β-Amyloid Peptide Activates Non-α7 Nicotinic Acetylcholine Receptors in Rat Basal Forebrain Neurons
Authors: Fu Wen , Jhamandas Jack H.
Published: May 2006

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by profound deficits in memory and cognitive function. Neuropathological hallmarks of the disease include a loss of basal forebrain cholinergic neurons and the deposition of β-amyloid peptide (Aβ) in neuritic plaques. At a cellular level, considerable attention has focused on a study of Aβ interactions with the neuronal nicotinic acetylcholine receptor (nAChR) subtypes. In this study, using cell-attached and outside-out single channel recordings from acutely dissociated rat basal forebrain neurons, we report that Aβ and nicotine activate nAChRs with two distinct levels of single-channel conductance. Whole cell recordings from these neurons reveal Aβ and nicotine, in a concentration-dependent and reversible manner, evoke brisk depolarizing responses and an inward current. The effects of Aβ on both single channel and whole cell are blocked by the noncompetitive nAChR antagonist mecamylamine and competitive nAChR antagonist dihydro-beta-erythroidine, but not the specific α7-selective nAChR antagonist methyllycaconitine, indicating that Aβ activated non-α7 nAChRs on basal forebrain neurons. In addition, the non-α7 nAChR agonists UB-165, epibatidine, and cytisine, but not the selective α7 agonist AR-R17779, induced similar responses as Aβ and nicotine. Thus non-α7 nAChRs may also represent a novel target in mediating the effects of Aβ in AD.
Excitatory Amino Acid Receptors of the Electrosensory System: The NR1/NR2BN-Methyl-d-Aspartate Receptor
Authors: Harvey-Girard Erik , Dunn Robert J.
Published: May 2006

The amino acid sequence of the N-methyl-d-aspartate (NMDA) receptor subunit NR2B from the brown ghost knife fish Apteronotus leptorhynchus has been determined and compared with the sequence of the murine NR2B. This comparison revealed high levels of sequence conservation throughout the ligand binding and membrane spanning segments. The functional properties of the NR1 and NR2B receptor complex were examined by coexpression in HEK cells. The recombinant AptNR1/NR2B receptors produced robust currents after stimulation with glutamate or NMDA in the presence of glycine. Measurements of the concentration dependencies for these agonists indicated that the agonist binding sites on the apteronotid receptor are highly conserved, with nearly identical agonist affinities to those of the murine NR1/NR2B receptor. The kinetic responses of the fish receptor were also highly conserved, with deactivation rates for the AptNR2B receptor matching those of the murine NR2B containing receptor. Evidently, most of the unique functional properties that reside in the NR2B receptor subunit have been well conserved in teleost NMDA receptors. On the other hand, the apteronitid receptor displayed a lowered sensitivity to voltage-dependent Mg2+block and a reduced affinity for the NR2B-specific noncompetitive antagonist ifenprodil. We conclude that the functional properties that result from the incorporation of the NR2B receptor in the NMDA receptor complex have been maintained since the evolutionary divergence of teleost and mammalian organisms.
State and Neuronal Class-Dependent Reconfiguration in the Avian Song System
Authors: Rauske Peter L. , Shea Stephen D. , Margoliash Daniel
Published: May 2006

Sensory systems may adapt to behavioral requirements through state-dependent changes. In the forebrain song-system nucleus HVc of zebra finches, state-dependent auditory responses have been described in multiunit recordings. Here we report on behavioral state-dependent changes in the activity of distinct HVc neuronal classes. HVc projection neurons were identified by electrically stimulating HVc's target nuclei, the robust nucleus of the archistriatum and Area X, in anesthetized zebra finches. Projection neurons and two classes of putative interneurons could be distinguished on the basis of extracellular spike waveforms, with the first two factors of a principal components analysis accounting for 81% of the variance in spike morphometric values. Spike width was the best single variable for distinguishing among the neuronal classes. Putative interneurons had much higher firing rates spontaneously and in response to song than did projection neurons, which had extremely low spontaneous rates and phasic responses to song. Recordings from HVc in behaving animals were dominated by the two classes of putative interneurons. Both classes showed strong, selective, and temporally similar auditory responses during sleep, but only one class of interneurons reliably maintained auditory responses on waking. These responses were weaker and less selective than those seen during sleep. The observation that HVc auditory responsiveness in awake zebra finches is restricted to some classes of neurons may help explain prior multiunit results that suggested nearly complete suppression of HVc auditory responses in awake birds. We propose that the heterogeneous effects of behavioral state on distinct subpopulations of HVc neurons allow HVc to participate in multiple roles during song production, conspecific song recognition, and possibly memory consolidation during sleep.
Block of Glutamate-Glutamine Cycle Between Astrocytes and Neurons Inhibits Epileptiform Activity in Hippocampus
Authors: Bacci Alberto , Sancini Giulio , Verderio Claudia , Armano Simona , Pravettoni Elena , Fesce Riccardo , Franceschetti Silvana , Matteoli Michela
Published: May 2006

Recurrent epileptiform activity occurs spontaneously in cultured CNS neurons and in brain slices in which GABA inhibition has been blocked. We demonstrate here that pharmacological treatments resulting in either the block of glutamine production by astrocytes or the inhibition of glutamine uptake by neurons suppress or markedly decrease the frequency of spontaneous epileptiform discharges both in primary hippocampal cultures and in disinhibited hippocampal slices. These data point to an important role for the neuron-astrocyte metabolic interaction in sustaining episodes of intense rhythmic activity in the CNS, and thereby reveal a new potential target for antiepileptic treatments.
Representation of Umami Taste in the Human Brain
Authors: de Araujo I.E.T. , Kringelbach M. L. , Rolls E. T. , Hobden P.
Published: May 2006

Umami taste stimuli, of which an exemplar is monosodium glutamate (MSG) and which capture what is described as the taste of protein, were shown using functional MRI (fMRI) to activate similar cortical regions of the human taste system to those activated by a prototypical taste stimulus, glucose. These taste regions included the insular/opercular cortex and the caudolateral orbitofrontal cortex. A part of the rostral anterior cingulate cortex (ACC) was also activated. When the nucleotide 0.005 M inosine 5′-monophosphate (IMP) was added to MSG (0.05 M), the blood oxygenation-level dependent (BOLD) signal in an anterior part of the orbitofrontal cortex showed supralinear additivity; this may reflect the subjective enhancement of umami taste that has been described when IMP is added to MSG. These results extend to humans previous studies in macaques showing that single neurons in these taste cortical areas can be tuned to umami stimuli.
Glycine Tranporter-1 Blockade Potentiates NMDA-Mediated Responses in Rat Prefrontal Cortical Neurons In Vitro and In Vivo
Authors: Chen Long , Muhlhauser Mark , Yang Charles R.
Published: May 2006

The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) has pivotal roles in neural development, learning, memory, and synaptic plasticity. Functional impairment of NMDA-R has been implicated in schizophrenia. NMDA-R activation requires glycine to act on the glycine-B (GlyB) site of the NMDA-R as an obligatory co-agonist with glutamate. Extracellular glycine near NMDA-R is regulated effectively by a glial glycine transporter (GlyT1). Using whole-cell voltage-clamp recordings in prefrontal cortex (PFC) slices, we have shown that exogenous GlyB site agonists glycine and d-serine, or a specific GlyT1 inhibitor N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl]sarcosine (NFPS) in the presence of exogenous glycine (10 μM), potentiated synaptically evoked NMDA excitatory postsynaptic currents (EPSCs) in vitro. Furthermore, in urethan-anesthetized rats, microiontophoretic NMDA pulses excite single PFC neurons. When these responses were blocked by approximately 50% to approximately 90% on continuous iontophoretic application of the GlyB site, antagonist (+)HA-966, intravenous NFPS (5 mg/kg), or a GlyB site agonist d-serine (50 mg/kg iv) reversed this (+)HA-966 block. NFPS may elevate endogenous glycine levels sufficiently to displace (+)HA-966 from the GlyB sites of the NMDA-R, thus enabling reactivation of the NMDA-Rs by iontophoretic NMDA applications. d-Serine (50–100 mg/kg iv) or NFPS (1–2 mg/kg iv) alone also augmented NMDA-evoked excitatory responses. These data suggest that direct GlyB site stimulation byd-serine, or blockade of GLYT1 to elevate endogenous glycine to act on unsaturated GlyB sites on NMDA-Rs, potentiated NMDA-R-mediated firing responses in rat PFC. Hence, blockade of GlyT1 to elevate glycine near the NMDA-R may activate hypofunctional NMDA-R, which has been implicated to play a critical role in the pathophysiology of schizophrenia.
NMDA Receptor-Dependent Long-Term Synaptic Depression in the Entorhinal Cortex In Vitro
Authors: Kourrich Saı̈d , Chapman C. Andrew
Published: May 2006

The entorhinal cortex receives a large projection from the piriform (primary olfactory) cortex and, in turn, provides the hippocampal formation with most of its cortical sensory input. Synaptic plasticity in this pathway may therefore affect the processing of olfactory information and memory encoding. We have recently found that long-term synaptic depression (LTD) can be induced in this pathway in vivo by repetitive paired-pulse stimulation but not by low-frequency (1 Hz) stimulation with single pulses. Here, we have used field potential recordings to investigate the stimulation parameters and transmitter receptors required for the induction of LTD in the rat entorhinal cortex in vitro. The effectiveness of low-frequency stimulation (900 pulses at 1 or 5 Hz) and repeated delivery of pairs of stimulation pulses (30-ms interpulse interval) was assessed. Only repeated paired-pulse stimulation resulted in lasting LTD, and a low-intensity paired-pulse stimulation protocol that induces LTD in vivo was only effective in the presence of the GABAAreceptor antagonist bicuculline (50 μM). LTD could also be induced in normal ACSF, however, by increasing the number of pulse-pairs delivered and by increasing the stimulation intensity during LTD induction. The induction of LTD was blocked by constant bath application of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovalerate (50 μM), indicating that LTD is dependent on NMDA receptor activation. However, LTD was not blocked by the group I/II mGluR antagonist (RS)-α-ethyl-4-carboxyphenylglycine (500 μM) or by bicuculline (50 μM). The induction of LTD in the entorhinal cortex in vitro is therefore dependent on intense stimulation that recruits activation of NMDA receptors, but does not require concurrent activation of mGluRs or inhibitory synaptic inputs.
Persistent Na+Current Modifies Burst Discharge By Regulating Conditional Backpropagation of Dendritic Spikes
Authors: Doiron Brent , Noonan Liza , Lemon Neal , Turner Ray W.
Published: May 2006

The estimation and detection of stimuli by sensory neurons is affected by factors that govern a transition from tonic to burst mode and the frequency chracteristics of burst output. Pyramidal cells in the electrosensory lobe of weakly electric fish generate spike bursts for the purpose of stimulus detection. Spike bursts are generated during repetitive discharge when a frequency-dependent broadening of dendritic spikes increases current flow from dendrite to soma to potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually triggers a somatic spike doublet with an interspike interval that falls inside the dendritic refractory period, blocking spike backpropagiation and the DAP. Repetition of this process gives rise to a rhythmic dendritic spike failure, termed conditional backpropagation, that converts cell output from tonic to burst discharge. Through in vitrorecordings and compartmental modeling we show that burst frequency is regulated by the rate of DAP potentiation during a burst, which determines the time required to discharge the spike doublet that blocks backpropagation. DAP potentiation is maginfied through a postitve feedback process when an increase in dendritic spike duration activates persistent sodium current ( INaP). INaPfurther promotes a slow depolarization that induces a shift from tonic to burst discharge over time. The results are consistent with a dynamical systems analysis that shows that the threshold separating tonic and burst discharge can be represented as a saddle-node bifurcation. The interaction between dendritic K+current and INaPprovides a physiological explanation for a variable time scale of bursting dynamics characteristic of such a bifurcation.
Baro-Activated Neurons With Pulse-Modulated Activity in the Rat Caudal Ventrolateral Medulla Express GAD67 mRNA
Authors: Schreihofer Ann M. , Guyenet Patrice G.
Published: May 2006

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are believed to mediate the sympathetic baroreceptor reflex by inhibiting presympathetic neurons in the rostral ventrolateral medulla (RVLM). Accordingly, some CVLM neurons are activated by increased arterial pressure (AP; baro-activated), have activity strongly modulated by the AP pulse (pulse-modulated), and can be antidromically activated from the RVLM. This study examined whether baro-activated, pulse-modulated CVLM neurons are indeed GABAergic and examined their structures. We recorded extracellularly from 19 baro-activated, pulse-modulated CVLM neurons in chloralose-anesthetized rats. Most of these cells (13/19) were silenced by decreasing AP with nitroprusside, but some (6/19) remained active at low AP levels. They were also excited by phenyl biguanide (17/17) but inhibited by noxious tail pinch (8/11). Twelve baro-activated cells were filled with biotinamide and examined for expression of GAD67 mRNA. Because adjacent vagal motor neurons are also activated by increased AP, we examined choline acetyltransferase (ChAT) immunoreactivity. Most baro-activated cells (9/12) expressed high levels of GAD67 mRNA, the rest (3/12) displayed lower levels of GAD67 mRNA, but none showed ChAT immunoreactivity. In contrast, adjacent baro-inhibited CVLM cells had no GAD67 mRNA ( n = 5) but were instead tyrosine hydroxylase immunoreactive ( n = 7). Reconstruction of baro-activated CVLM neurons revealed axons that projected dorsomedially and rostrally with several axon collaterals. These data demonstrate the existence of GABAergic CVLM neurons with the physiological characteristics expected of interneurons that mediate the sympathetic baroreceptor reflex. In addition, baro-activated GABAergic CVLM neurons appear to integrate several types of inputs and provide inhibition to multiple targets.
Afferent Innervation Patterns of the Saccule in Pigeons
Authors: Zakir M. , Huss D. , Dickman J. D.
Published: May 2006

The innervation patterns of vestibular saccular afferents were quantitatively investigated in pigeons using biotinylated dextran amine as a neural tracer and three-dimensional computer reconstruction. Type I hair cells were found throughout a large portion of the macula, with the highest density observed in the striola. Type II hair cells were located throughout the macula, with the highest density in the extrastriola. Three classes of afferent innervation patterns were observed, including calyx, dimorph, and bouton units, with 137 afferents being anatomically reconstructed and used for quantitative comparisons. Calyx afferents were located primarily in the striola, innervated a number of type I hair cells, and had small innervation areas. Most calyx afferent terminal fields were oriented parallel to the anterior-posterior axis and the morphological polarization reversal line. Dimorph afferents were located throughout the macula, contained fewer type I hair cells in a calyceal terminal than calyx afferents and had medium sized innervation areas. Bouton afferents were restricted to the extrastriola, with multi-branching fibers and large innervation areas. Most of the dimorph and bouton afferents had innervation fields that were oriented dorso-ventrally but were parallel to the neighboring reversal line. The organizational morphology of the saccule was found to be distinctly different from that of the avian utricle or lagena otolith organs and appears to represent a receptor organ undergoing evolutionary adaptation toward sensing linear motion in terrestrial and aerial species.
Responses to Taste Stimulation in the Ventroposteromedial Nucleus of the Thalamus in Rats
Authors: Verhagen Justus V. , Giza Barbara K. , Scott Thomas R.
Published: May 2006

Extracellular action potentials were recorded from 73 neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of the whole oral cavity. The stimulus array consisted of 16 room-temperature (23°C) sapid stimuli, distilled water at three temperatures (0, 23, and 37°C), and 0.1 M NaCl at three temperatures (0, 23, and 37°C). Among all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to taste and temperature, none to taste and touch, but 6% to all three modalities. Discharge rates evoked by the basic tastants were 13.8 ± 1.6 (SD) spikes/s for 0.1 M NaCl, 9.3 ± 1.4 spikes/s for 0.01 M HCl, 5.1 ± 0.9 spikes/s for 0.5 M sucrose, and 4.3 ± 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean responses at 0, 23, and 37°C of 9.9 ± 1.5, 0.6 ± 0.4, and 1.3 ± 0.9 spikes/s, respectively. The mean firing rate evoked by 37 and 0°C NaCl was 15.0 ± 2.4 and 17.0 ± 2.8 spikes/s, respectively. The exponent of the NaCl concentration-response power function was 0.39. Thalamic taste cells were broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory cells was 0.79 ± 0.02. Two cells responded predominantly with inhibition, which accounted for the majority of inhibitory responses. The taste neurons were statistically divisible into three groups: sodium-oriented ( n = 40), acid-oriented ( n = 12), and sugar-oriented ( n = 17). Four additional bitter-oriented neurons were not closely enough related to be defined as a group and were considered outliers. The sodium-oriented group could be divided into three statistically distinct subgroups, differing in the specificity of their responses to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response rates, signal-to-noise ratio, proportions of cells responding best to basic tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc neurons have characteristics that are intermediate between those of parabrachial and cortical gustatory neurons.
Intact Synaptic GABAergic Inhibition and Altered Neurosteroid Modulation of Thalamic Relay Neurons in Mice Lacking δ Subunit
Authors: Porcello Darrell M. , Huntsman Molly M. , Mihalek Robert M. , Homanics Gregg E. , Huguenard John R.
Published: May 2006

Robust GABA-mediated inhibitory postsynaptic currents (IPSCs) in neurons of the thalamic relay (TC) nuclei are important in sustaining oscillatory activity within thalamic and thalamocortical circuits. The biophysical properties and pharmacological sensitivities of these IPSCs both depend on the subunit combination of postsynaptic γ-aminobutyric acid-A (GABAA) receptors. Recombinant GABAAreceptors containing the δ subunit (heavily expressed in TC nuclei) have been shown to exhibit slowed desensitization rates and high affinity for GABA in heterologous expression systems. We tested whether the GABAA-mediated synaptic inhibition in TC neurons would be affected by loss of the δ subunit. Spontaneous and evoked IPSCs were recorded from neurons in the ventral basal complex (VB) of the thalamus from brain slices of wild-type (δ+/+) and homozygous δ subunit deficient mice (δ−/−). Spontaneous IPSCs (sIPSCs) from δ−/−mice had no significant differences in amplitude, duration, or frequency compared with their δ+/+counterparts. However, baseline noise (63% of control) and the relative contribution of the slow component to overall decay (79% of control) were significantly lower in δ−/−VB recordings. Evoked IPSCs (eIPSCs) in δ−/−neurons showed no difference in peak amplitude, but had an accelerated slow decay component (40- vs. 55-ms time constant). We further tested whether neurosteroid modulation of GABAAreceptors was dependent on the presence of the δ subunit, as previously reported in recombinant systems. Pregnenolone sulfate (PS) significantly reduced eIPSC peak amplitude (−30%) and increased duration in δ−/−, but not in δ+/+mice. sIPSCs were not affected in any neurons, δ−/−or δ+/+. In contrast, 3-alpha,5-alpha-tetrahydrodeoxycorticosterone (THDOC) increased the durations of eIPSCs and sIPSCs in both δ−/−and δ+/+VB neurons. Our findings show that although the δ subunit confers a striking PS insensitivity to eIPSCs in VB neurons, it plays only a minor role in the synaptic inhibition of VB neurons. This suggests δ subunit containing GABAAreceptors may be functionally limited to an extrasynaptic locus in VB neurons.
Strychnine-Sensitive Glycine Receptors Depress Hyperexcitability in Rat Dentate Gyrus
Authors: Chattipakorn Siriporn C. , McMahon Lori L.
Published: May 2006

Previously we have shown that strychnine-sensitive glycine-gated chloride channels (GlyRs) are functionally expressed by CA1 pyramidal cells and GABAergic interneurons in mature rat hippocampal slices. We now report that glycine application to dentate granule cells and hilar interneurons recorded in acute slices from adolescent rats elicits a strychnine-sensitive current similar to glycine-mediated currents recorded in area CA1, indicating that GlyRs are also present on neurons in the dentate gyrus. This finding suggests that GlyRs have a widespread distribution in the hippocampal region. The physiological role of GlyRs in forebrain is unclear, but it is possible that these receptors mediate neuronal inhibition, similar to γ-aminobutyric acid-A (GABAA) receptors and thus could be a novel target for antiepileptic therapy. Therefore we tested the hypothesis that activation of inhibitory GlyRs could suppress neuronal hyperexcitability in dentate, a brain region vulnerable to epileptic activity. In whole-cell current-clamp recordings of granule cells, we observed a membrane potential hyperpolarization followed by cessation of the action potential firing pattern in hyperexcitable slices induced by elevated extracellular K+or by blocking GABAAreceptors with bicuculline. The GlyR antagonist, strychnine, prevented the antiepileptic effect of glycine. These results demonstrate that glycine, acting at GlyRs, elicits neuronal inhibition in dentate. Further, our findings suggest the possibility that these receptors could be a therapeutic target for the treatment of epilepsy.
Allopregnanolone Activates GABAAReceptor/Cl−Channels in a Multiphasic Manner in Embryonic Rat Hippocampal Neurons
Authors: Liu Qi-Ying , Chang Yoong H. , Schaffner Anne E. , Smith Susan V. , Barker Jeffery L.
Published: May 2006

Although 3α-substituted metabolites of progesterone are well established to interact with GABAAreceptor/Cl−channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABAAreceptor/Cl−channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABAAreceptor subunits. Allopregnanolone primarily induced multiphasic current responses in neurons, which were eliminated by bicuculline, an antagonist of GABA at GABAAreceptor/Cl−channels. Similar multiphasic responses blocked by bicuculline were induced by allopregnanollone in nonneuronal cells transfected with α1and γ2subunits, indicating that the steroid activation of GABAAreceptor/Cl−channels occurred independently of GABA. Fluctuation analyses of current responses to allopregnanolone and GABA revealed underlying channel activities with similar estimated unitary properties. However, although both agonists activated Cl−channels with similar estimated short and long burst-length durations, most of those stimulated by the steroid were short, while most of those opened by GABA were long. Allopregnanolone potentiated GABA-evoked Cl−currents in nonneuronal cells transfected with α1and β2or β3subunits, which did not exhibit multiphasic responses to the steroid, indicating another, independent action of the steroid at activated receptors. Pertussis toxin treatment eliminated the low-amplitude current and attenuated the high-amplitude current induced by allopregnanolone in a reversible manner. Mastoparan, which activates G proteins directly, triggered a high-amplitude current after a delay, which was blocked by bicuculline. The results indicate that allopregnanolone interacts with GABAAreceptor/Cl−channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins.
Augmentation of Plasticity of the Central Auditory System by the Basal Forebrain and/or Somatosensory Cortex
Authors: Ma Xiaofeng , Suga Nobuo
Published: May 2006

Auditory conditioning (associative learning) or focal electric stimulation of the primary auditory cortex (AC) evokes reorganization (plasticity) of the cochleotopic (frequency) map of the inferior colliculus (IC) as well as that of the AC. The reorganization results from shifts in the best frequencies (BFs) and frequency-tuning curves of single neurons. Since the importance of the cholinergic basal forebrain for cortical plasticity and the importance of the somatosensory cortex and the corticofugal auditory system for collicular and cortical plasticity have been demonstrated, Gao and Suga proposed a hypothesis that states that the AC and corticofugal system play an important role in evoking auditory collicular and cortical plasticity and that auditory and somatosensory signals from the cerebral cortex to the basal forebrain play an important role in augmenting collicular and cortical plasticity. To test their hypothesis, we studied whether the amount and the duration of plasticity of both collicular and cortical neurons evoked by electric stimulation of the AC or by acoustic stimulation were increased by electric stimulation of the basal forebrain and/or the somatosensory cortex. In adult big brown bats ( Eptesicus fuscus), we made the following major findings. 1) Collicular and cortical plasticity evoked by electric stimulation of the AC is augmented by electric stimulation of the basal forebrain. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 2) Collicular and cortical plasticity evoked by AC stimulation is augmented by somatosensory cortical stimulation mimicking fear conditioning. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 3) Collicular and cortical plasticity evoked by both AC and basal forebrain stimulations is further augmented by somatosensory cortical stimulation. 4) A lesion of the basal forebrain tends to reduce collicular and cortical plasticity evoked by AC stimulation. The reduction is small and statistically insignificant for collicular plasticity but significant for cortical plasticity. 5) The lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. 6) Collicular and cortical plasticity evoked by repetitive acoustic stimuli is augmented by basal forebrain and/or somatosensory cortical stimulation. However, the lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. These findings support the hypothesis proposed by Gao and Suga.
Binocular Deficits Associated With Early Alternating Monocular Defocus. I. Behavioral Observations
Authors: Wensveen Janice M. , Harwerth Ronald S. , Smith Earl L.
Published: May 2006

To study the binocular vision deficits associated with anisometropia, monkeys were reared with alternating monocular defocus, which allowed monocular mechanisms to develop normally while binocular mechanisms were selectively compromised. A defocusing contact lens of –1.5 D, –3 D, or –6 D was worn on alternate eyes on successive days ( n = 3 per lens power) from 3 wk to 9 mo of age. The control subjects were two normally reared monkeys and two human observers. Functional binocular vision was assessed through behavioral measurements of stereoscopic depth discrimination thresholds as a function of spatial frequency. To characterize the extent of the deficits in disparity processing at a given spatial frequency, the contrast required to support stereopsis was determined for a range of disparities that exceeded the subjects' measured stereoacuity. The lens-reared monkeys showed spatial-frequency-selective deficits in stereopsis that depended on the magnitude of the simulated anisometropia experienced during the rearing period. For a given spatial frequency, the treated monkeys generally required higher than normal contrasts to support stereopsis even for large disparities. Moreover, a given increase in contrast produced smaller than normal improvements in stereo discrimination in our treated subjects, which suggests that in addition to deficits in contrast sensitivity, disparity-sensitive mechanisms exhibited low contrast gains. The spatial-frequency selective nature of the binocular deficits produced by the imposed anisometropia indicate that disparity processing mechanisms are normally spatial-frequency selective and that mechanisms tuned to different spatial frequencies can be differentially affected by abnormal binocular visual experience.
Neural Basis of Visually Guided Head Movements Studied With fMRI
Authors: Petit Laurent , Beauchamp Michael S.
Published: May 2006

We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus. These areas have been previously observed in functional imaging studies of human eye movements, suggesting that a common set of brain areas subserves both oculomotor and head movement control in humans, consistent with data from single-unit recording and microstimulation studies in nonhuman primates that have described overlapping eye- and head-movement representations in oculomotor control areas. A second set of areas was active during head and gaze movements but not during eye movements. This set of areas included the posterior part of the planum temporale and the cortex at the temporoparietal junction, known as the parieto-insular vestibular cortex (PIVC). Activity in PIVC has been observed during imaging studies of invasive vestibular stimulation, and we confirm its role in processing the vestibular cues accompanying natural head movements. Our findings demonstrate that fMRI can be used to study the neural basis of head movements and show that areas that control eye movements also control head movements. In addition, we provide the first evidence for brain activity associated with vestibular input produced by natural head movements as opposed to invasive caloric or galvanic vestibular stimulation.