bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage-Activated Currents From Adult Honeybee (Apis mellifera) Antennal Motor Neurons Recorded In Vitro and In Situ
Authors: Kloppenburg P. , Kirchhof B. S. , Mercer A. R.
Published: December 2017

Kloppenburg, P., B. S. Kirchhof, and A. R. Mercer. Voltage-activated currents from adult honeybee ( Apis mellifera) antennal motor neurons recorded in vitro and in situ. J. Neurophysiol. 81: 39–48, 1999. Voltage-activated currents from adult honey bee antennal motor neurons were characterized with in vitro studies in parallel with recordings taken from cells in situ. Two methods were used to ensure unequivocal identification of cells as antennal motor neurons: 1) selective backfilling of the neurons with fluorescent markers before dissociation for cell culture or before recording from cells in intact brains, semiintact brains, or in brain slices or 2) staining with a fluorescent marker via the patch pipette during recordings and identifying antennal motor neurons in situ on the basis of their characteristic morphology. Four voltage-activated currents were isolated in these antennal motor neurons with pharmacological, voltage, and ion substitution protocols. The neurons expressed at least two distinct K+currents, a transient current ( IA) that was blocked by 4-aminopyridine (4–5 × 10−3M), and a sustained current ( IK( V)) that was partially blocked by tetraethylammonium (2–3 × 10−2M) and quinidine (5 × 10−5M). IAactivated above −40 to −30 mV and the half-maximal voltages for steady-state activation and inactivation were −8.8 and −43.2 mV, respectively. IK( V)activated above −50 to −40 mV and the midpoint of the steady-state activation curve was +11.2 mV. IK( V)did not show steady-state inactivation. Additionally, two inward currents were isolated: a tetrodotoxin (10−7M)-sensitive, transient Na+current ( INa) that activated above −35 mV, with a maximum around −5 mV and a half-maximal voltage for inactivation of −72.6 mV, and a CdCl2(5 × 10−5M)-sensitive Ca2+current that activated above −45 to −40 mV, with a maximum around −15 mV. This study represents the first step in our effort to analyze the cellular and ionic mechanisms underlying the intrinsic properties and plasticity of antennal motor neurons.
Neuromodulation of Dendritic Action Potentials
Authors: Hoffman Dax A. , Johnston Daniel
Published: December 2017

Hoffman, Dax A. and Daniel Johnston. Neuromodulation of dendritic action potentials. J. Neurophysiol. 81: 408–411, 1999. The extent to which regenerative action potentials invade hippocampal CA1 pyramidal dendrites is dependent on both recent activity and distance from the soma. Previously, we have shown that the amplitude of back-propagating dendritic action potentials can be increased by activating either protein kinase A (PKA) or protein kinase C (PKC) and a subsequent depolarizing shift in the activation curve for dendritic K+ channels. Physiologically, an increase in intracellular PKA and PKC would be expected upon activation of β-adrenergic and muscarinic acetylcholine receptors, respectively. Accordingly, we report here that activation of either of these neurotransmitter systems results in an increase in dendritic action-potential amplitude. Activation of the dopaminergic neurotransmitter system, which is also expected to raise intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) and PKA levels, increased action-potential amplitude in only a subpopulation of neurons tested.
Extracellular Chloride and the Maintenance of Spontaneous Epileptiform Activity in Rat Hippocampal Slices
Authors: Hochman Daryl W. , D'Ambrosio Raimondo , Janigro Damir , Schwartzkroin Philip A.
Published: December 2017

Hochman, Daryl W., Raimondo D'Ambrosio, Damir Janigro, and Philip A. Schwartzkroin. Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. J. Neurophysiol. 81: 49–59, 1999. Previous studies showed that furosemide blocks spontaneous epileptiform activity without diminishing synaptic transmission or reducing hyperexcited field responses to electrical stimuli. We now test the hypothesis that the antiepileptic effects of furosemide are mediated through its blockade of the Na+,K+,2Cl− cotransporter and thus should be mimicked by a reduction of extracellular chloride ([Cl−]o). In the first set of experiments, field recordings from the CA1 cell body layer of hippocampal slices showed that spontaneous bursting developed within 10–20 min in slices perfused with low-[Cl−]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a further 10–20 min. Intracellular recordings from CA1 pyramidal cells showed that normal action potential discharge could be elicited by membrane depolarization, even after the tissue was perfused with low-[Cl−]o medium for >2 h. In a second set of experiments, spontaneous bursting activity was induced in slices by perfusion with high-[K+]o (10 mM), bicuculline (100 μM), or 4-aminopyridine (100 μM). In each case, recordings from the CA1 region showed that reduction of [Cl−]o to 21 mM reversibly blocked the bursting within 1 h. Similar to previous observations with furosemide treatment, low-[Cl−]o medium blocked spontaneous hypersynchronous discharges without reducing synaptic hyperexcitability (i.e., hyperexcitable field responses evoked by electrical stimulation). In a third set of experiments, prolonged exposure (>1 h after spontaneous bursting ceased) of slices to systematically varied [Cl−]o and [K+]o resulted in one of three types of events: 1) spontaneous, long-lasting, and repetitive negative field potential shifts (7 mM [Cl−]o; 3 mM [K+]o); 2) oscillations consisting of 5- to 10-mV negative shifts in the field potential, with a period of ∼1 cycle/40 s (16 mM [Cl−]o; 12 mM [K+]o); and 3) shorter, infrequently occurring negative field shifts lasting 20–40 s (21 mM [Cl−]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl−]o on neuronal synchronization and spontaneous discharge are time dependent. Similar effects were seen with furosemide and low [Cl−]o, consistent with the hypothesis that the antiepileptic effect of furosemide is mediated by the drug's effect on chloride transporters. Finally, the results of altering extracellular potassium along with chloride suggest that blockade of the Na+, K+,2Cl− cotransporter, which normally transports chloride from the extracellular space into glial cells, is key to these antiepileptic effects.
Electrophysiological Evidence for Tetrodotoxin-Resistant Sodium Channels in Slowly Conducting Dural Sensory Fibers
Authors: Strassman A. M. , Raymond S. A.
Published: December 2017

Electrophysiological evidence for tetrodotoxin-resistant sodium channels in mechanosensitive nerve endings of slowly conducting fibers in the intracranial dura. A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 μM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-δ units [conduction velocity (c.v.) 5–18 m/s] but only 50% (5/10) of slow A-δ units (1.5 <c.v.<5 m/s) and 13% (2/15) of C units (c.v. ≤1.5 m/s). The mean TTX concentration that produced complete suppression of mechanoresponsiveness was ∼270-fold higher in C units than in fast A-δ units. In contrast, no significant difference was found between C and A-δ units in the concentration of lidocaine required for complete suppression of mechanoresponsiveness, indicating that the greater TTX resistance of mechanoresponsiveness in C units is not attributable to differences in safety factor unrelated to channel subtype. These data offer indirect evidence that a TTX-resistant channel subtype is expressed in the terminal axonal branches of many of the more slowly conducting (C and slow A-δ) dural afferents. The channel appears to be present in these fibers, but not in the faster A-δ fibers, in sufficient numbers to support the initiation and propagation of mechanically induced impulses. Comparison with previous data on the absence of TTX resistance in peripheral nerve fibers suggests that the TTX-resistant sodium channel may be a distinctive feature of the receptive rather than the conductive portion of the sensory neuron’s axonal membrane.
Activation of Metabotropic Glutamate Receptors Modulates the Voltage-Gated Sustained Calcium Current in a Teleost Horizontal Cell
Authors: Linn Cindy L. , Gafka Adele C.
Published: December 2017

Activation of metabotropic glutamate receptors modulates the voltage-gated sustained calcium current in a teleost horizontal cell. In the teleost retina, cone horizontal cells contain a voltage-activated sustained calcium current, which has been proposed to be involved in visual processing. Recently, several studies have demonstrated that modulation of voltage-gated channels can occur through activation of metabotropic glutamate receptors (mGluRs). Because glutamate is the excitatory neurotransmitter in the vertebrate retina, we have used whole cell electrophysiological techniques to examine the effect of mGluR activation on the sustained voltage-gated calcium current found in isolated cone horizontal cells in the catfish retina. In pharmacological conditions that blocked voltage-gated sodium and potassium channels, as well as N-methyl-d-aspartate (NMDA) and non-NMDA channels, application of l-glutamate or 1-aminocyclopentane-1,3-dicarboxylic acid (1 S,3 R-ACPD) to voltage-clamped cone horizontal cells acted to increase the amplitude of the calcium current, expand the activation range of the calcium current by 10 mV into the cell’s physiological operating range, and shift the peak calcium current by −5 mV. To identify and characterize the mGluR subtypes found on catfish cone horizontal cells, agonists of group I, group II, or group III mGluRs were applied via perfusion. Group I and group III mGluR agonists mimicked the effect of l-glutamate or 1 S,3 R-ACPD, whereas group II mGluR agonists had no effect on L-type calcium current activity. Inhibition studies demonstrated that group I mGluR antagonists significantly blocked the modulatory effect of the group I mGluR agonist, ( S)-3,5-dihydroxyphenylglycine. Similar results were obtained when the group III mGluR agonist,l-2-amino-4-phosphonobutyric acid, was applied in the presence of a group III mGluR antagonist. These results provide evidence for two groups of mGluR subtypes on catfish cone horizontal cells. Activation of these mGluRs is linked to modulation of the voltage-gated sustained calcium current.
C-PR Neuron ofAplysiaHas Differential Effects on “Feeding” Cerebral Interneurons, Including Myomodulin-Positive CBI-12
Authors: Hurwitz Itay , Perrins Ray , Xin Yuanpei , Weiss Klaudiusz R. , Kupfermann Irving
Published: December 2017

C-PR neuron of Aplysia has differential effects on “feeding” cerebral interneurons, including myomodulin-positive CBI-12. Head lifting and other aspects of the appetitive central motive state that precedes consummatory feeding movements in Aplysia is promoted by excitation of the C-PR neuron. Food stimuli activate C-PR as well as a small population of cerebral-buccal interneurons (CBIs). We wished to determine if firing of C-PR produced differential effects on the various CBIs or perhaps affected all the CBIs uniformly as might be expected for a neuron involved in producing a broad undifferentiated arousal state. We found that when C-PR was fired, it produced a wide variety of effects on various CBIs. Firing of C-PR evoked excitatory input to a newly identified CBI (CBI-12) the soma of which is located in the M cluster near the previously identified CBI-2. CBI-12 shares certain properties with CBI-2, including a similar morphology and a capacity to drive rhythmic activity of the buccal-ganglion. Unlike CBI-2, CBI-12 exhibits myomodulin immunoreactivity. Furthermore when C-PR is fired, CBI-12 receives a polysynaptic voltage-dependent slow excitation, whereas, CBI-2 receives relatively little input. C-PR also polysynaptically excites other CBIs including CBI-1 and CBI-8/9 but produces inhibition in CBI-3. In addition, firing of C-PR inhibits plateau potentials in CBI-5/6. The data suggest that activity of C-PR may promote the activity of one subset of cerebral-buccal interneurons, perhaps those involved in ingestive behaviors that occur during the head-up posture. C-PR also inhibits some cerebral-buccal interneurons that may be involved in behaviors in which C-PR activity is not required or may even interfere with other feeding behaviors such as rejection or grazing, that occur with the head down.
Source of Inappropriate Receptive Fields in Cortical Somatotopic Maps From Rats That Sustained Neonatal Forelimb Removal
Authors: Lane Richard D. , Stojic Rey S. , Killackey Herbert P. , Rhoades Robert W.
Published: December 2017

Source of inappropriate receptive fields in cortical somatotopic maps from rats that sustained neonatal forelimb removal. Previously this laboratory demonstrated that forelimb removal at birth in rats results in the invasion of the cuneate nucleus by sciatic nerve axons and the development of cuneothalamic cells with receptive fields that include both the forelimb-stump and the hindlimb. However, unit-cluster recordings from primary somatosensory cortex (SI) of these animals revealed few sites in the forelimb-stump representation where responses to hindlimb stimulation also could be recorded. Recently we reported that hindlimb inputs to the SI forelimb-stump representation are suppressed functionally in neonatally amputated rats and that GABAergic inhibition is involved in this process. The present study was undertaken to assess the role that intracortical projections from the SI hindlimb representation may play in the functional reorganization of the SI forelimb-stump field in these animals. The SI forelimb-stump representation was mapped during γ-aminobutyric acid (GABA)-receptor blockade, both before and after electrolytic destruction of the SI hindlimb representation. Analysis of eight amputated rats showed that 75.8% of 264 stump recording sites possessed hindlimb receptive fields before destruction of the SI hindlimb. After the lesions, significantly fewer sites (13.2% of 197) were responsive to hindlimb stimulation ( P < 0.0001). Electrolytic destruction of the SI lower-jaw representation in four additional control rats with neonatal forelimb amputation did not significantly reduce the percentage of hindlimb-responsive sites in the SI stump field during GABA-receptor blockade ( P = 0.98). Similar results were obtained from three manipulated rats in which the SI hindlimb representation was silenced temporarily with a local cobalt chloride injection. Analysis of response latencies to sciatic nerve stimulation in the hindlimb and forelimb-stump representations suggested that the intracortical pathway(s) mediating the hindlimb responses in the forelimb-stump field may be polysynaptic. The mean latency to sciatic nerve stimulation at responsive sites in the GABA-receptor blocked SI stump representation of neonatally amputated rats was significantly longer than that for recording sites in the hindlimb representation [26.3 ± 8.1 (SD) ms vs. 10.8 ± 2.4 ms, respectively, P < 0.0001]. These results suggest that hindlimb input to the SI forelimb-stump representation detected in GABA-blocked cortices of neonatally forelimb amputated rats originates primarily from the SI hindlimb representation.
Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation
Authors: Yang Shao-Nian , Tang Yun-Gui , Zucker Robert S.
Published: December 2017

Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation. Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.
Blockade of Hippocampal Long-Term Potentiation by Sustained Tetanic Stimulation Near the Recording Site
Authors: Kauer Julie A.
Published: December 2017

Blockade of hippocampal long-term potentiation by sustained tetanic stimulation near the recording site. Specific patterns of electrical stimulation trigger several forms of synaptic plasticity in hippocampal pyramidal cells, including a long-term potentiation (LTP) of excitatory synaptic transmission. I investigated the effect of commonly used stimulation protocols at different distances from the recording site. Sustained electrical stimulation (100 Hz, 1 s) delivered close to the recording site prevented LTP induction; the same stimulation from a second electrode placed farther away subsequently produced LTP at the same recording site. Strong stimulation near the recording site could also interfere with LTP triggered from a distal site. In contrast to sustained high-frequency stimulation, intermittent stimulation (θ burst pattern) delivered close to the recording site produced normal LTP. These data support the hypothesis that strong stimulation releases a factor that acts locally to prevent LTP.
Recovery of the Vestibulocolic Reflex After Aminoglycoside Ototoxicity in Domestic Chickens
Authors: Goode Christopher T. , Carey John P. , Fuchs Albert F. , Rubel Edwin W
Published: December 2017

Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in domestic chickens. Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was ∼35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.
Central Processing of Pulsed Pheromone Signals by Antennal Lobe Neurons in the Male Moth Agrotis segetum
Authors: Lei H. , Hansson B. S.
Published: December 2017

Central processing of pulsed pheromone signals by antennal lobe neurons in the male moth Agrotis segetum. Male moths use female-produced pheromones as orientation cues during the mate-finding process. In addition to the needs of evaluating the quality and quantity of the pheromone signal, the male moth also needs to resolve the filamentous structure of the pheromone plume to proceed toward the releasing point successfully. To understand how a discontinuous olfactory signal is processed at the central level, we used intracellular recording methods to characterize the response patterns of antennal lobe (AL) neurons to pulsatile stimulation with the full female-produced pheromone blend and its single components in male turnip moths, Agrotis segetum. Air puffs delivered at frequencies of 1, 3, 5, 7, or 10 Hz were used to carry the stimulus. Two types of AL neurons were characterized according to their capabilities to resolve stimulus pulses. The most common type could resolve at least 1-Hz pulses, thus termed fast neurons; another type could not resolve any pulses, thus termed slow neurons. When fast neurons were excited by stimuli, they always displayed biphasic response patterns, a depolarization phase followed by a hyperpolarization phase. This pattern could be evoked by stimulation with both the single pheromone components and the blend. The pulse-resolving capability of the fast neurons correlated significantly with the size of the hyperpolarization phase. When the amplitude was higher and the fall time of the hyperpolarization faster, the neuron could follow more pulses per second. Moreover, interactions between different pheromone components eliciting different response patterns did not improve the pulse-resolving capability of fast neurons.
Quantal Secretion and Nerve-Terminal Cable Properties at Neuromuscular Junctions in an Amphibian (Bufo marinus)
Authors: Macleod G. T. , Farnell L. , Gibson W. G. , Bennett M. R.
Published: December 2017

Quantal secretion and nerve-terminal cable properties at neuromuscular junctions in an amphibian ( Bufo marinus). The effect of a conditioning depolarizing current pulse (80–200 μs) on quantal secretion evoked by a similar test pulse at another site was examined in visualized motor-nerve terminal branches of amphibian endplates ( Bufo marinus). Tetrodotoxin (200 nM) and cadmium (50 μM) were used to block voltage-dependent sodium and calcium conductances. Quantal release at the test electrode was depressed at different distances (28–135 μm) from the conditioning electrode when the conditioning and test pulses were delivered simultaneously. This depression decreased when the interval between conditioning and test current pulses was increased, until, at an interval of ∼0.25 ms, it was negligible. At no time during several thousand test-conditioning pairs, for electrodes at different distances apart (28–135 μm) on the same or contiguous terminal branches, did the electrotonic effects of quantal release at one electrode produce quantal release at the other. Analytic and numerical solutions were obtained for the distribution of transmembrane potential at different sites along terminal branches of different lengths for current injection at a point on a terminal branch wrapped in Schwann cell, in the absence of active membrane conductances. Solutions were also obtained for the combined effects of two sites of current injection separated by different time delays. This cable model shows that depolarizing current injections of a few hundred microseconds duration produce hyperpolarizations at ∼30 μm beyond the site of current injection, with these becoming larger and occurring at shorter distances the shorter the terminal branch. Thus the effect of a conditioning depolarizing pulse at one site on a subsequent test pulse at another more than ∼30 μm away is to substantially decrease the absolute depolarization produced by the latter, provided the interval between the pulses is less than a few hundred microseconds. It is concluded that the passive cable properties of motor nerve terminal branches are sufficient to explain the effects on quantal secretion by a test electrode depolarization of current injections from a spatially removed conditioning electrode.
Patterns of Phrenic Motor Output Evoked by Chemical Stimulation of Neurons Located in the Pre-Bötzinger Complex In Vivo
Authors: Solomon Irene C. , Edelman Norman H. , Neubauer Judith A.
Published: December 2017

Patterns of phrenic motor output evoked by chemical stimulation of neurons located in the pre-Bötzinger complex in vivo. The pre-Bötzinger complex (pre-BötC) has been proposed to be essential for respiratory rhythm generation from work in vitro. Much less, however, is known about its role in the generation and modulation of respiratory rhythm in vivo. Therefore we examined whether chemical stimulation of the in vivo pre-BötC manifests respiratory modulation consistent with a respiratory rhythm generator. In chloralose- or chloralose/urethan-anesthetized, vagotomized cats, we recorded phrenic nerve discharge and arterial blood pressure in response to chemical stimulation of neurons located in the pre-BötC with dl-homocysteic acid (DLH; 10 mM; 21 nl). In 115 of the 122 sites examined in the pre-BötC, unilateral microinjection of DLH produced an increase in phrenic nerve discharge that was characterized by one of the following changes in cycle timing and pattern: 1) a rapid series of high-amplitude, rapid rate of rise, short-duration bursts, 2) tonic excitation (with or without respiratory oscillations), 3) an integration of the first two types of responses (i.e., tonic excitation with high-amplitude, short-duration bursts superimposed), or 4) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a high-amplitude, short-duration burst). In 107 of these sites, the phrenic neurogram response was accompanied by an increase or decrease (≥10 mmHg) in arterial blood pressure. Thus increases in respiratory burst frequency and production of tonic discharge of inspiratory output, both of which have been seen in vitro, as well as modulation of burst pattern can be produced by local perturbations of excitatory amino acid neurotransmission in the pre-BötC in vivo. These findings are consistent with the proposed role of this region as the locus for respiratory rhythm generation.
Inhibitory Contributions to Spatiotemporal Receptive-Field Structure and Direction Selectivity in Simple Cells of Cat Area 17
Authors: Murthy Aditya , Humphrey Allen L.
Published: December 2017

Inhibitory contributions to spatiotemporal receptive-field structure and direction selectivity in simple cells of cat area 17. Intracortical inhibition contributes to direction selectivity in primary visual cortex, but how it acts has been unclear. We investigated this problem in simple cells of cat area 17 by taking advantage of the link between spatiotemporal (S-T) receptive-field structure and direction selectivity. Most cells in layer 4 have S-T–oriented receptive fields in which gradients of response timing across the field confer a preferred direction of motion. Linear summation of responses across the receptive field, followed by a static nonlinear amplification, has been shown previously to account for directional tuning in layer 4. We tested the hypotheses that inhibition acts by altering S-T structure or the static nonlinearity or both. Drifting and counterphasing sinewave gratings were used to measure direction selectivity and S-T structure, respectively, in 17 layer 4 simple cells before and during iontophoresis of bicuculline methiodide (BMI), a GABAA antagonist. S-T orientation was quantified from fits to response temporal phase versus stimulus spatial phase data. Bicuculline reduced direction selectivity and S-T orientation in nearly all cells, and reductions in the two measures were well correlated ( r = 0.81) and reversible. Using conventional linear predictions based on response phase and amplitude, we found that BMI-induced changes in S-T structure also accounted well for absolute changes in the amplitude and phase of responses to gratings drifting in the preferred and nonpreferred direction. For each cell we also calculated an exponent used to estimate the static nonlinearity. Bicuculline reduced the exponent in most cells, but the changes were not correlated with reductions in direction selectivity. We conclude that GABAA-mediated inhibition influences directional tuning in layer 4 primarily by sculpting S-T receptive-field structure. The source of the inhibition is likely to be other simple cells with certain spatiotemporal relationships to their target. Despite reductions in the two measures, most receptive fields maintained some directional tuning and S-T orientation during BMI. This suggests that their excitatory inputs, arising from the lateral geniculate nucleus and within area 17, are sufficient to create some S-T orientation and that inhibition accentuates it. Finally, BMI also reduced direction selectivity in 8 of 10 simple cells tested in layer 6, but the reductions were not accompanied by systematic changes in S-T structure. This reflects the fact that S-T orientation, as revealed by our first-order measures of the receptive field, is weak there normally. Inhibition likely affects layer 6 cells via more complex, nonlinear interactions.
Electrophysiological Properties of Rat Phrenic Motoneurons During Perinatal Development
Authors: Martin-Caraballo Miguel , Greer John J.
Published: December 2017

Electrophysiological properties of rat phrenic motoneurons during perinatal development. Past studies determined that there is a critical period at approximately embryonic day (E)17 during which phrenic motoneurons (PMNs) undergo a number of pivotal developmental events, including the inception of functional recruitment via synaptic drive from medullary respiratory centers, contact with spinal afferent terminals, the completion of diaphragm innervation, and a major transformation of PMN morphology. The objective of this study was to test the hypothesis that there would be a marked maturation of motoneuron electrophysiological properties occurring in conjunction with these developmental processes. PMN properties were measured via whole cell patch recordings with a cervical slice–phrenic nerve preparation isolated from perinatal rats. From E16 to postnatal day 1, there was a considerable transformation in a number of motoneuron properties, including 1) 10-mV increase in the hyperpolarization of the resting membrane potential, 2) threefold reduction in the input resistance, 3) 12-mV increase in amplitude and 50% decrease duration of action potential, 4) major changes in the shapes of potassium- and calcium-mediated afterpotentials, 5) decline in the prominence of calcium-dependent rebound depolarizations, and 6) increases in rheobase current and steady-state firing rates. Electrical coupling among PMNs was detected in 15–25% of recordings at all ages studied. Collectively, these data and those from parallel studies of PMN–diaphragm ontogeny describe how a multitude of regulatory mechanisms operate in concert during the embryonic development of a single mammalian neuromuscular system.
Effect of Hypertonicity on Augmentation and Potentiation and on Corresponding Quantal Parameters of Transmitter Release
Authors: Cheng Hong , Miyamoto Michael D.
Published: December 2017

Effect of hypertonicity on augmentation and potentiation and on corresponding quantal parameters of transmitter release. Augmentation and (posttetanic) potentiation are two of the four components comprising the enhanced release of transmitter following repetitive nerve stimulation. To examine the quantal basis of these components under isotonic and hypertonic conditions, we recorded miniature endplate potentials (MEPPs) from isolated frog ( Rana pipiens) cutaneous pectoris muscles, before and after repetitive nerve stimulation (40 s at 80 Hz). Continuous recordings were made in low Ca2+ high Mg2+ isotonic Ringer solution, in Ringer that was made hypertonic with 100 mM sucrose, and in wash solution. Estimates were obtained of m (no. of quanta released), n (no. of functional release sites), p (mean probability of release), and vars p (spatial variance in p), using a method that employed MEPP counts. Hypertonicity abolished augmentation without affecting potentiation. There were prolonged poststimulation increases in m, n,and p and a marked but transient increase in vars p in the hypertonic solution. All effects were completely reversed with wash. The time constants of decay for potentiation and for vars p were virtually identical. The results are consistent with the notion that augmentation is caused by Ca2+ influx through voltage-gated calcium channels and that potentiation is due to Na+-induced Ca2+ release from mitochondria. The results also demonstrate the utility of this approach for analyzing the dynamics of quantal transmitter release.
Characterization of a Na+-Dependent Betaine Transporter With Cl−Channel Properties in Squid Motor Neurons
Authors: Petty Christopher N. , Lucero Mary T.
Published: December 2017

Characterization of a Na+-dependent betaine transporter with Cl−channel properties in squid motor neurons. Most marine invertebrates, including squids, use transporters to accumulate organic osmolytes such as betaine, to prevent water loss when exposed to elevated salinity. Although a limited number of flux studies have shown the Na+dependence of betaine transport, nothing is known about the electrogenic properties of osmolyte transporters. We used whole cell and perforated-patch voltage-clamp techniques to characterize the electrical properties of the betaine transporter in giant fiber lobe motor neurons of the squid Lolliguncula brevis. Betaine activated a large, Cl−-selective current that was reversibly blocked by 100 μM niflumic acid (97 ± 2% block after 40 s, SD; n = 7) and partially inhibited by 500 μM SITS (29 ± 11%; n = 5). The Cl−current was Na+dependent and was virtually eliminated by isotonic replacement of Na+with Li+, NMDG+, or Tris+. Concentration-response data revealed an EC50in a physiologically relevant range for these animals of 5.1 ± 0.9 mM ( n = 11). In vertebrates, the betaine transporter is structurally related to the GABA transporter, and although GABA did not directly activate the betaine-induced current, it reversibly reduced betaine responses by 34 ± 14% ( n = 8). Short-term changes in osmolality alone did not activate the Cl−current, but when combined with betaine, Cl−currents increased in hypertonic solutions and decreased in hypotonic solutions. Activation of the betaine transporter and Cl−current in hypertonic conditions may affect both volume regulation and excitability in L. brevis motor neurons. This study is the first report of a novel betaine transporter in neurons that can act as a Cl−channel.
Glutamate Regulates IP3-Type and CICR Stores in the Avian Cochlear Nucleus
Authors: Kato B. Maya , Rubel Edwin W
Published: December 2017

Glutamate regulates IP3-type and CICR stores in the avian cochlear nucleus. Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are activated by glutamate released from auditory nerve terminals. If this stimulation is removed, the intracellular calcium ion concentration ([Ca2+]i) of NM neurons rises and rapid atrophic changes ensue. We have been investigating mechanisms that regulate [Ca2+]iin these neurons based on the hypothesis that loss of Ca2+homeostasis causes the cascade of cellular changes that results in neuronal atrophy and death. In the present study, video-enhanced fluorometry was used to monitor changes in [Ca2+]istimulated by agents that mobilize Ca2+from intracellular stores and to study the modulation of these responses by glutamate. Homobromoibotenic acid (HBI) was used to stimulate inositol trisphosphate (IP3)-sensitive stores, and caffeine was used to mobilize Ca2+from Ca2+-induced Ca2+release (CICR) stores. We provide data indicating that Ca2+responses attributable to IP3- and CICR-sensitive stores are inhibited by glutamate, acting via a metabotropic glutamate receptor (mGluR). We also show that activation of C-kinase by a phorbol ester will reduce HBI-stimulated calcium responses. Although the protein kinase A accumulator, Sp-cAMPs, did not have an effect on HBI-induced responses. CICR-stimulated responses were not consistently attenuated by either the phorbol ester or the Sp-cAMPs. We have previously shown that glutamate attenuates voltage-dependent changes in [Ca2+]i. Coupled with the present findings, this suggests that in these neurons mGluRs serve to limit fluctuations in intracellular Ca2+rather than increase [Ca2+]i. This system may play a role in protecting highly active neurons from calcium toxicity resulting in apoptosis.
Oculomotor Tracking in Two Dimensions
Authors: Engel Kevin C. , Anderson John H. , Soechting John F.
Published: December 2017

Oculomotor tracking in two dimensions. Results from studies of oculomotor tracking in one dimension have indicated that saccades are driven primarily by errors in position, whereas smooth pursuit movements are driven primarily by errors in velocity. To test whether this result generalizes to two-dimensional tracking, we asked subjects to track a target that moved initially in a straight line then changed direction. We found that the general premise does indeed hold true; however, the study of oculomotor tracking in two dimensions provides additional insight. The first saccade was directed slightly in advance of target location at saccade onset. Thus its direction was related primarily to angular positional error. The direction of the smooth pursuit movement after the saccade was related linearly to the direction of target motion with an average slope of 0.8. Furthermore the magnitude and direction of smooth pursuit velocity did not change abruptly; consequently the direction of smooth pursuit appeared to rotate smoothly over time.
Citrate Ions Enhance Taste Responses to Amino Acids in the Largemouth Bass
Authors: Ogawa K. , Caprio J.
Published: December 2017

Citrate ions enhance taste responses to amino acids in the largemouth bass. The glossopharyngeal (IX) taste system of the largemouth bass, Micropterus salmoides, is highly selective to amino acids and is poorly responsive to trisodium citrate; however, IX taste responses to specific concentrations of l- andd-arginine and l-lysine but notl-proline were enhanced by citrate but not sodium ions. Binary mixtures of l-arginine (3 × 10−4M and 10−3 M) or d-arginine (10−3M) + trisodium citrate (10−3 M; pH 7–9) resulted in enhanced taste activity, whereas binary mixtures of higher concentrations (10−2 M and 10−1 M) ofl- or d-arginine + 10−3 M trisodium citrate were not significantly different from the response to the amino acid alone. Under continuous adaptation to 10−3M citrate, taste responses to l-arginine were also enhanced at the identical concentrations previously indicated, but responses to 10−2 M and 10−1 Ml-arginine were significantly suppressed. Under continuous adaptation to 10−2 M l-arginine, taste responses to 10−2 M, 10−1 M, and 100 M citrate were significantly enhanced. Cellular concentrations of both citrate and amino acids in prey of the carnivorous largemouth bass are sufficient for this taste-enhancing effect to occur naturally during consummatory feeding behavior. Citrate acting as a calcium chelator is presented as a possible mechanism of action for the enhancement effect.
Opioidergic Modulation of Voltage-Activated K+Currents in Magnocellular Neurons of the Supraoptic Nucleus in Rat
Authors: Müller Wolfgang , Hallermann Stephan , Swandulla Dieter
Published: December 2017

Opioidergic modulation of voltage-activated K+ currents in magnocellular neurons of the supraoptic nucleus in rat. Opioidergic modulation plays an important role in the control of oxytocin and vasopressin release by magnocellular neurons (MCNs) in the supraoptic and paraventricular nuclei of the hypothalamus. We have used whole cell patch-clamp recording in acute slices of the supraoptic nucleus (SON) of the hypothalamus to study opioidergic modulation of voltage-dependent K+ currents in MCNs that are involved in release activity. The μ-receptor agonistd-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO, 2 μM) affected K+currents in 55% of magnocellular neurons recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed rectifier current ( I K(V)) amplitude by ∼50% without significant effects on its activation kinetics. The transient A current ( I A) was enhanced by DAMGO by ∼36%. Its inactivation kinetic was accelerated slightly while the voltage dependence of steady-state inactivation was shifted by −6 mV to more negative potentials. All DAMGO effects were blocked by the preferential non-κ-opioid antagonist naloxone (10 μM). The κ-opioid agonist trans-(±)-3,4-dichloro- N-methyl- N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 μM) strongly suppressed I K(V) by ∼57% and evoked a 20-mV hyperpolarizing shift and an acceleration of activation in both, DAMGO-sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced I A by ∼29% and τ of inactivation by −20% in DAMGO-sensitive cells. In contrast, in DAMGO-insensitive cells U50,488 increased I A by ∼23% and strongly accelerated inactivation (τ −44%). The effects of U50,488 were suppressed by the selective κ-receptor antagonist nor-binaltorphimine (5 μM). We conclude that μ- and κ-opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulation of voltage-dependent K+ currents. In vasopressinergic MCNs, κ-opioidergic inputs differentially modulate these K+currents. The modulation of K+ currents is assumed to significantly contribute to opioidergic control of hormone release by MCNs within the supraoptic nucleus and from the axon terminals in the neural lobe.
Somatostatin Acts in CA1 and CA3 to Reduce Hippocampal Epileptiform Activity
Authors: Tallent Melanie K. , Siggins George R.
Published: December 2017

Somatostatin acts in CA1 and CA3 to reduce hippocampal epileptiform activity. Although the peptide somatostatin (SST) has been speculated to function in temporal lobe epilepsy, its exact role is unclear, as in vivo studies have suggested both pro- and anticonvulsant properties. We have shown previously that SST has multiple inhibitory cellular actions in the CA1 region of the hippocampus, suggesting that in this region SST should have antiepileptic actions. To directly assess the effect of SST on epileptiform activity, we studied two in vitro models of epilepsy in the rat hippocampal slice preparation using extracellular and intracellular recording techniques. In one, GABA-mediated neurotransmission was inhibited by superfusion of the GABAA receptor antagonist bicuculline. In the second, we superfused Mg2+-free artificial cerebrospinal fluid to remove the Mg2+ block of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor. We show here that SST markedly reduces the intensity of evoked epileptiform afterdischarges and the frequency of spontaneous bursts in both CA1 and CA3. SST appears to act additively in the two regions to suppress the transmission of epileptiform events through the hippocampus. We further examined SST’s actions in CA3 and found that SST dramatically reduced the frequency of paroxysmal depolarizing shifts (PDSs) recorded intracellularly in current clamp, as well as increasing the threshold for evoking “giant” excitatory postsynaptic currents (EPSCs), large polysynaptically mediated EPSCs that are the voltage-clamp correlate of PDSs. We also examined the actions of SST on pharmacologically isolated EPSCs generated at both mossy fiber (MF) and associational/commissural (A/C) synapses. SST appears to act specifically to reduce recurrent excitation between CA3 neurons because it depresses A/C- but not MF-evoked EPSCs. SST also increased paired-pulse facilitation of A/C EPSCs, suggesting a presynaptic site of action. Reciprocal activation of CA3 neurons through A/C fibers is critical for generation of epileptiform activity in hippocampus. Thus SST reduces feedforward excitation in rat hippocampus, acting to “brake” hyperexcitation. This is a function unique from that described for other hippocampal neuropeptides, which affect more standard neurotransmission. Our results suggest that SST receptors could be a unique, selective clinical target for treatment of limbic seizures.
Impulse Encoding Across the Dendritic Morphologies of Retinal Ganglion Cells
Authors: Sheasby Brent W. , Fohlmeister Jurgen F.
Published: December 2017

Impulse encoding across the dendritic morphologies of retinal ganglion cells. Nerve impulse entrainment and other excitation and passive phenomena are analyzed for a morphologically diverse and exhaustive data set ( n = 57) of realistic (3-dimensional computer traced) soma-dendritic tree structures of ganglion cells in the tiger salamander ( Ambystoma tigrinum) retina. The neurons, including axon and an anatomically specialized thin axonal segment that is observed in every ganglion cell, were supplied with five voltage- or ligand-gated ion channels (plus leakage), which were distributed in accordance with those found in a recent study that employed an equivalent dendritic cylinder. A wide variety of impulse-entrainment responses was observed, including regular low-frequency firing, impulse doublets, and more complex patterns involving impulse propagation failures (or aborted spikes) within the encoder region, all of which have been observed experimentally. The impulse-frequency response curves of the cells fell into three groups called fast, medium, andslow in approximate proportion as seen experimentally. In addition to these, a new group was found among the traced cells that exhibited an impulse-frequency response twice that of thefast category. The total amount of soma-dendritic surface area exhibited by a given cell is decisive in determining its electrophysiological classification. On the other hand, we found only a weak correlation between the electrophysiological group and the morphological classification of a given cell, which is based on the complexity of dendritic branching and the physical reach or “receptive field” area of the cell. Dendritic morphology determines discharge patterns to dendritic (synaptic) stimulation. Orthodromic impulses can be initiated on the axon hillock, the thin axonal segment, the soma, or even the proximal axon beyond the thin segment, depending on stimulus magnitude, soma-dendritic membrane area, channel distribution, and state within the repetitive impulse cycle. Although a sufficiently high dendritic Na-channel density can lead to dendritic impulse initiation, this does not occur with our “standard” channel densities and is not seen experimentally. Even so, impulses initiated elsewhere do invade all except very thin dendritic processes. Impulse-encoding irregularities increase when channel conductances are reduced in the encoder region, and the F/I properties of the cells are a strong function of the calcium- and Ca-activated K-channel densities. Use of equivalent dendritic cylinders requires more soma-dendritic surface area than real dendritic trees, and the source of the discrepancy is discussed.