bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Properties of GABAAReceptor–Mediated Signaling During Early Neocortical Development
Authors: Owens David F. , Liu Xiaolin , Kriegstein Arnold R.
Published: December 2017

Evidence from several brain regions suggests γ-aminobutyric acid (GABA) can exert a trophic influence during development, expanding the role of this amino acid beyond its function as an inhibitory neurotransmitter. Proliferating precursor cells in the neocortical ventricular zone (VZ) express functional GABAAreceptors as do immature postmigratory neurons in the developing cortical plate (CP); however, GABAAreceptor properties in these distinct cell populations have not been compared. Using electrophysiological techniques in embryonic and early postnatal neocortex, we find that GABAAreceptors expressed by VZ cells have a higher apparent affinity for GABA and are relatively insensitive to receptor desensitization compared with neurons in the CP. GABA-induced current magnitude increases with maturation with the smallest responses found in recordings from precursor cells in the VZ. No evidence was found that GABAAreceptors on VZ cells are activated synaptically, consistent with previous data suggesting that these receptors are activated in a paracrine fashion by nonsynaptically released ligand. After neurons are born and migrate to the CP, they begin to demonstrate spontaneous synaptic activity, the majority of which is GABAAmediated. These spontaneous GABAApostsynaptic currents (sPSCs) first were detected at embryonic day 18 (E18). At birth, ∼50% of recordings from cortical neurons demonstrated GABAA-mediated sPSCs, and this value increased with age. GABAA-mediated sPSCs were action potential dependent and arose from local GABAergic interneurons. GABA application could evoke action potential–dependent PSCs in neonatal cortical neurons, suggesting that during the first few postnatal days, GABA can act as an excitatory neurotransmitter. Finally, N-methyl-d-aspartate (NMDA)- but not non-NMDA-mediated sPSCs were also present in early postnatal neurons. These events were not observed in cells voltage clamped at negative holding potentials (−60 to −70 mV) but were evident when the holding potential was set at positive values (+30 to +60 mV). Together these results provide evidence for the early maturation of GABAergic communication in the neocortex and a functional change in GABAA-receptor properties between precursor cells and early postmitotic neurons. The change in GABAA-receptor properties may reflect the shift from paracrine to synaptic receptor activation.
Whole-Muscle and Motor-Unit Contractile Properties of the Styloglossus Muscle in Rat
Authors: Sutlive Thomas G. , McClung J. Ross , Goldberg Stephen J.
Published: December 2017

Investigations of whole muscle and motor-unit contractile properties have provided valuable information for our understanding of the spinal cord and extraocular motor systems. However, no previous investigation has examined these properties in an isolated tongue muscle. The purpose of this study was to determine the contractile properties and muscle fiber types of the rat styloglossus muscle. The styloglossus is one of three extrinsic tongue muscles and serves to retract the tongue within the oral cavity. Adult male Sprague-Dawley rats ( n = 19) were used in these experiments. The contractile characteristics of the whole styloglossus muscle ( n = 9) were measured in response to stimulation of the hypoglossal nerve branch to the muscle. The average twitch tension produced was 3.30 g with a mean twitch contraction time of 13.81 ms. The mean maximum tetanic tension was 19.66 g and occurred at or near the fusion frequency, which averaged 109 Hz. The styloglossus muscle was resistant to fatigue [fatigue index (F. I.) = 0.76]. In separate experiments ( n = 7), the contractile characteristics of 37 single motor units were measured in response to extracellular stimulation of hypoglossal motoneurons. The twitch tension generated by styloglossus motor units averaged 35.7 mg, and the mean twitch contraction time was 12.46 ms. The mean fusion frequency was 92 Hz. Maximum tetanic tension averaged 177.8 mg. Styloglossus single motor units were resistant to fatigue (F. I. = 0.74). The sites of stimulation that yielded a contractile response in the styloglossus muscle were consistent with the location of the styloglossus motoneuron pool reported in earlier anatomy studies. Muscle fiber typing was determined in three animals based on the myofibrillar ATPase reaction at pH 9.8, 4.6, and 4.3. The styloglossus muscle was composed of ≈99% type IIA fibers with a few scattered type I fibers present in the study sample. On the basis of the combined findings of the physiology and histochemistry experiments, the styloglossus muscle appeared to be a homogeneous muscle composed almost exclusively of fast, fatigue-resistant motor units. These properties of the styloglossus muscle and its motor units were compared with findings in other rat skeletal muscles.
Behavioral Thermosensitivity After Lesions of Thalamic Target Areas of a Thermosensory Spinothalamic Pathway in the Cat
Authors: Norrsell U. , Craig A. D.
Published: December 2017

The ability of 17 cats to discriminate floor temperatures 2–4°C below the ambient temperature was tested before and after unilateral electrolytic thalamic lesions. The lesions were made contralateral to the paws showing better performance in the temperature discrimination task. They were aimed at one or more of the three main target areas of thermoreceptive-specific lamina I spinothalamic neurons [i.e., the nucleus submedius, the dorsomedial aspect of the ventral posterior medial nucleus, and the ventral aspect of the basal ventral medial nucleus (vVMb)], following microelectrode mapping of somatosensory thalamus. The thermosensory consequences of each lesion were measured in postoperative testing, beginning 6–8 days after the final preoperative test session. A mild but definite thermosensory deficiency was found in five cats, in which the response behavior on the contralateral side was reduced below the 69% criterion level for several sessions. Histological analysis indicated that these cats differed only by the inclusion in the lesion of all or part of vVMb. Consequently this area appears to be important for cats’ thermosensory behavior. Nevertheless even large lesions of virtually all of the thermoreceptive lamina I spinothalamic projection areas produced only this mild thermosensory deficit in stark contrast with the massive defect observed previously after spinal lesions of the middle of the lateral funiculus, where lamina I axons ascend. Accordingly such spinal lesions were added at the C4 level, on the same side as the thalamic lesions, in six cats 3 mo after the thalamic surgery. These lesions caused severe contralateral defects (i.e., chance level performance). Thus the present findings are taken to indicate that contralateral ascending projections to vVMb in the thalamus participate in cats’ thermosensory discrimination but that ascending projections to the brain stem must play an important role in their behavioral thermosensitivity.
Effects of Metabotropic Glutamate Receptor Activation in Auditory Thalamus
Authors: Tennigkeit Frank , Schwarz Dietrich W. F. , Puil Ernest
Published: December 2017

Metabotropic glutamate receptors (mGluRs) are expressed predominantly in dendritic regions of neurons of auditory thalamus. We studied the effects of mGluR activation in neurons of the ventral partition of medial geniculate body (MGBv) using whole cell current- and voltage-clamp recordings in brain slices. Bath application of the mGluR-agonist, 1S,3R-1-aminocyclopentan-1,3-dicarboxylic acid or 1S,3R-ACPD (5–100 μM), depolarized MGBv neurons ( n = 67), changing evoked response patterns from bursts to tonic firing as well as frequency responses from resonance (∼1 Hz) to low-pass filter characteristics. The depolarization was resistant to Na+-channel blockade with tetrodotoxin (TTX; 300 nM) and Ca2+-channel blockade with Cd2+(0.1 mM). The application of 1S,3R-ACPD did not change input conductance and produced an inward current ( I ACPD) with an average amplitude of 84.2 ± 5.3 pA (at −70 mV, n = 22). The application of the mGluR antagonist, (RS)-α-methyl-4-carboxyphenylglycine (0.5 mM), reversibly blocked the depolarization or I ACPD. During intracellular application of guanosine 5′- O-(3-thiotriphosphate) from the recording electrode, bath application of 1S,3R-ACPD irreversibly activated a large amplitude I ACPD. During intracellular application of guanosine 5′- O-(2-thiodiphosphate), application of 1S,3R-ACPD evoked only a small I ACPD. These results implicate G proteins in mediation of the 1S,3R-ACPD response. A reduction of external [Na+] from 150 to 26 mM decreased I ACPD to 32.8 ± 10.3% of control. Internal applications of a Ca2+ chelator, 1,2-bis-(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid (BAPTA; 10 mM), suppressed I ACPD, implying a contribution of a Ca2+ signal or Na+/Ca2+ exchange. However, partial replacement of Na+ with Li+ (50 mM) did not significantly change I ACPD. Therefore it seemed less likely that a Na+/Ca2+ exchange current was a major participant in the response. A reduction of extracellular [K+] from 5.25 to 2.5 mM or external Ba2+(0.5 mM) or Cs+ (2 mM) did not significantly change I ACPD between −40 and −85 mV. Below −85 mV, 1S,3R-ACPD application reversibly attenuated an inward rectification, displayed by 11 of 20 neurons. Blockade of an inwardly rectifying K+ current with Ba2+ (1 mM) or Cs+ (2–3 mM) occluded the attenuation. In the range positive to −40 mV, 1S,3R-ACPD application activated an outward current which Cs+ blocked; this unmasked a voltage dependence of the inward I ACPD with a maximum amplitude at ∼−30 mV. The I ACPDproperties are consistent with mGluR expression as a TTX-resistant, persistent Na+ current in the dendritic periphery. We suggest that mGluR activation changes the behavior of MGBv neurons by three mechanisms: activation of a Na+-dependent inward current; activation of an outward current in a depolarized range; and inhibition of the inward rectifier, I KIR. These mechanisms differ from previously reported mGluR effects in the thalamus.
Effects of Noradrenaline on Locomotor Rhythm–Generating Networks in the Isolated Neonatal Rat Spinal Cord
Authors: Kiehn Ole , Sillar Keith T. , Kjaerulff Ole , McDearmid Jonathan R.
Published: December 2017

We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5–50 μM) elicited either no measurable root activity, or activity of a highly variable nature. When present, the NA-induced activity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony between antagonistic motor pools. Finally, in a few cases, NA induced a slow locomotor-like rhythm, in which activity alternated between the left and right sides, and between rostral and caudal roots on the same side. As shown previously, stable locomotor activity could be induced by bath application of N-methyl-d-aspartate (NMDA; 4–8.5 μM) and/or serotonin (5-HT; 4–20 μM). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1–5 μM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background activity of the ongoing rhythm. Moreover, NA did not obviously affect the left/right and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT locomotor rhythm sometimes displayed a time-dependent breakdown in coordination, ultimately resulting in tonic ventral root activity. However, the addition of NA to the NMDA/5-HT saline could reinstate a well-coordinated locomotor rhythm. We conclude that exogenously applied NA can elicit tonic activity or can trigger a slow, irregular and often synchronous motor pattern. When NA is applied during ongoing locomotor activity, the amine has a distinct slowing effect on the rhythm while preserving the normal coordination between flexors and extensors. The ability of NA to “rescue” rhythmic locomotor activity after its time-dependent deterioration suggests that the amine may be important in the maintenance of rhythmic motor activity.
Electrophysiological Roles of L-Type Channels in Different Classes of Guinea Pig Sympathetic Neuron
Authors: Davies Philip J. , Ireland David R. , Martinez-Pinna Juan , McLachlan Elspeth M.
Published: December 2017

The electrophysiological consequences of blocking Ca2+ entry through L-type Ca2+ channels have been examined in phasic ( Ph), tonic ( T), and long-afterhyperpolarizing ( LAH) neurons of intact guinea pig sympathetic ganglia isolated in vitro. Block of Ca2+entry with Co2+ or Cd2+ depolarized T and LAH neurons, reduced action potential (AP) amplitude in Ph and LAHneurons, and increased AP half-width in Ph neurons. The afterhyperpolarization (AHP) and underlying Ca2+-dependent K+ conductances ( gKCa1 and gKCa2) were reduced markedly in all classes. Addition of 10 μM nifedipine increased input resistance in LAHneurons, raised AP threshold in Ph and LAH neurons, and caused a small increase in AP half-width in Ph neurons. AHP amplitude and the amplitude and decay time constant of gKCa1 were reduced by nifedipine in all classes; the slower conductance, gKCa2, which underlies the prolonged AHP in LAH neurons, was reduced by 40%. Surprisingly, AHP half-width was lengthened by nifedipine in a proportion of neurons in all classes; despite this, neuron excitability was increased during a maintained depolarization. Nifedipine’s effects on AHP half-width were not mimicked by 2 mM Cs+ or 2 mM anthracene-9-carboxylic acid, a blocker of Cl− channels, and it did not modify transient outward currents of the A or D types. The effects of 100 μM Ni2+ differed from those of nifedipine. Thus in Ph neurons, Ca2+ entry through L-type channels during a single action potential contributes to activation of K+ conductances involved in both the AP and AHP, whereas in T and LAH neurons, it acts only on gKCa1 and gKCa2. These results differ from the results in rat superior cervical ganglion neurons, in which L-type channels are selectively coupled to BK channels, and in hippocampal neurons, in which L-type channels are selectively coupled to SK channels. We conclude that the sources of Ca2+ for activating the various Ca2+-activated K+conductances are distinct in different types of neuron.
Effects of Large Excitatory and Inhibitory Inputs on Motoneuron Discharge Rate and Probability
Authors: Türker K. S. , Powers R. K.
Published: December 2017

We elicited repetitive discharge in hypoglossal motoneurons recorded in slices of rat brain stem using a combination of a suprathreshold injected current step with superimposed noise to mimic the synaptic drive likely to occur during physiological activation. The effects of repetitive en mass stimulation of afferent nerves were simulated by the further addition of trains of injected current transients of varying shapes and sizes. The effects of a given current transient on motoneuron discharge timing and discharge rate were measured by calculating a peristimulus time histogram (PSTH) and a peristimulus frequencygram (PSF). The amplitude and time course of the simulated postsynaptic potentials (PSPs) produced by the current transients were calculated by convolving the current transient with an estimate of the passive impulse response of the motoneuron. We then compared the shape of the injected current transient and the simulated PSP to the profiles of the PSTH and the PSF records. The PSTHs produced by excitatory PSPs (EPSPs) were characterized by a large, short-latency increase in firing probability that lasted slightly longer than the rising phase of the EPSP, followed by a reduced discharge probability during the falling phase of the EPSP. In contrast, the PSF analysis revealed a proportionate increase in discharge rate over the entire profile of the EPSP, even though relatively few spikes occurred during the falling phase. The PSTHs associated with inhibitory PSPs (IPSPs) indicated a reduction in discharge probability during the initial, hyperpolarizing phase of the IPSP, followed by an increase in the discharge probability during its subsequent repolarizing phase. Using the PSF analysis, the initial phase of the IPSP appeared as a large hole in the record where a very small number or no discharges occurred. The subsequent phase of the IPSP was associated with frequency values that were lower than the background values. The primary features of both PSTHs and PSFs can be used to estimate the relative amplitudes of the underlying EPSPs and IPSPs. However, PSTHs contain secondary peaks and troughs that are not directly related to the underlying PSP but instead reflect the regular recurrence of spikes following those affected by the PSP. The PSF analysis is more useful for indicating the total duration and the profile of the underlying PSP. The shape of the underlying PSP can be obtained directly from the PSF records because the discharge frequency of the spikes follow the PSPs very closely, especially for EPSPs.
Spatial Alignment of Rotational and Static Tilt Responses of Vestibulospinal Neurons in the Cat
Authors: Perlmutter S. I. , Iwamoto Y. , Baker J. F. , Peterson B. W.
Published: December 2017

The responses of vestibulospinal neurons to 0.5-Hz, whole-body rotations in three-dimensional space and static tilts of whole-body position were studied in decerebrate and alert cats. The neurons’ spatial properties for earth-vertical rotations were characterized by maximum and minimum sensitivity vectors ( R max and R min) in the cat’s horizontal plane. The orientation of a neuron’s R max was not consistently related to the orientation of its maximum sensitivity vector for static tilts ( T max). The angular difference between R max and T max was widely distributed between 0° and 150°, and R max and T max were aligned (i.e., within 45° of each other) for only 44% (14/32) of the neurons. The alignment of R max and T max was not correlated with the neuron’s sensitivity to earth-horizontal rotations, or to the orientation of R max in the horizontal plane. In addition, the extent to which a neuron exhibited spatiotemporal convergent (STC) behavior in response to vertical rotations was independent of the angular difference between R max and T max. This suggests that the high incidence of STC responses in our sample (56%) reflects not only canal-otolith convergence, but also the presence of static and dynamic otolith inputs with misaligned directionality. The responses of vestibulospinal neurons reflect a complex combination of static and dynamic vestibular inputs that may be required by postural reflexes that vary depending on head, trunk, and limb orientation, or on the frequency of stimulation.
Neural Mechanisms for Processing Binocular Information I. Simple Cells
Authors: Anzai Akiyuki , Ohzawa Izumi , Freeman Ralph D.
Published: December 2017

The visual system integrates information from the left and right eyes and constructs a visual world that is perceived as single and three dimensional. To understand neural mechanisms underlying this process, it is important to learn about how signals from the two eyes interact at the level of single neurons. Using a sophisticated receptive field (RF) mapping technique that employs binary m-sequences, we have determined the rules of binocular interactions exhibited by simple cells in the cat’s striate cortex in relation to the structure of their monocular RFs. We find that binocular interaction RFs of most simple cells are well described as the product of left and right eye RFs. Therefore the binocular interactions depend not only on binocular disparity but also on monocular stimulus position or phase. The binocular interaction RF is consistent with that predicted by a model of a linear binocular filter followed by a static nonlinearity. The static nonlinearity is shown to have a shape of a half-power function with an average exponent of ∼2. Although the initial binocular convergence of signals is linear, the static nonlinearity makes binocular interaction multiplicative at the output of simple cells. This multiplicative binocular interaction is a key ingredient for the computation of interocular cross-correlation, an algorithm for solving the stereo correspondence problem. Therefore simple cells may perform initial computations necessary to solve this problem.
Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro
Authors: Iribe Yuji , Moore Kevin , Pang Kevin C. H. , Tepper James M.
Published: December 2017

The subthalamic nucleus (STN) is one of the principal sources of excitatory glutamatergic input to dopaminergic neurons of the substantia nigra, yet stimulation of the STN produces both excitatory and inhibitory effects on nigral dopaminergic neurons recorded extracellularly in vivo. The present experiments were designed to determine the sources of the excitatory and inhibitory effects. Synaptic potentials were recorded intracellularly from substantia nigra pars compacta dopaminergic neurons in parasagittal slices in response to stimulation of the STN. Synaptic potentials were analyzed for onset latency, amplitude, duration, and reversal potential in the presence and absence of GABA and glutamate receptor antagonists. STN-evoked depolarizing synaptic responses in dopaminergic neurons reversed at approximately −31 mV, intermediate between the expected reversal potential for an excitatory and an inhibitory postsynaptic potential (EPSP and IPSP). Blockade of GABAA receptors with bicuculline caused a positive shift in the reversal potential to near 0 mV, suggesting that STN stimulation evoked a near simultaneous EPSP and IPSP. Both synaptic responses were blocked by application of the glutamate receptor antagonist, 6-cyano-7-nitroquinoxalene-2,3-dione. The confounding influence of inhibitory fibers of passage from globus pallidus and/or striatum by STN stimulation was eliminated by unilaterally transecting striatonigral and pallidonigral fibers 3 days before recording. The reversal potential of STN-evoked synaptic responses in dopaminergic neurons in slices from transected animals was approximately −30 mV. Bath application of bicuculline shifted the reversal potential to ∼5 mV as it did in intact animals, suggesting that the source of the IPSP was within substantia nigra. These data indicate that electrical stimulation of the STN elicits a mixed EPSP-IPSP in nigral dopaminergic neurons due to the coactivation of an excitatory monosynaptic and an inhibitory polysynaptic connection between the STN and the dopaminergic neurons of substantia nigra pars compacta. The EPSP arises from a direct monosynaptic excitatory glutamatergic input from the STN. The IPSP arises polysynaptically, most likely through STN-evoked excitation of GABAergic neurons in substantia nigra pars reticulata, which produces feed-forward GABAA-mediated inhibition of dopaminergic neurons through inhibitory intranigral axon collaterals.
Relative Roles of the S Cell Network and Parallel Interneuronal Pathways in the Whole-Body Shortening Reflex of the Medicinal Leech
Authors: Shaw Brian K. , Kristan William B.
Published: December 2017

The whole-body shortening reflex of the medicinal leech Hirudo medicinalis is a withdrawal response produced by anterior mechanical stimuli. The interneuronal pathways underlying this reflex consist of the S cell network (a chain of electrically coupled interneurons) and a set of other, parallel pathways. We used a variety of techniques to characterize these interneuronal pathways further, including intracellular stimulation of the S cell network, photoablation of the S cell axon, and selective lesions of particular connectives (the axon bundles that link adjacent ganglia in the leech nerve cord). These experiments demonstrated that the S cell network is neither sufficient nor necessary for the production of the shortening reflex. The axons of the parallel pathways were localized to the lateral connectives (whereas the S cell axon runs through the medial connective). We used physiological techniques to show that the axons of the parallel pathways have a larger diameter in the anterior connective and to demonstrate that the parallel pathways are activated selectively by anterior mechanosensory stimuli. We also presented correlative evidence that the parallel pathways, along with activating motor neurons during shortening, are responsible for inhibiting a higher-order “command-like” interneuron in the neuronal circuit for swimming, thus playing a role in the behavioral choice between swimming and shortening.
Horizontal Vestibuloocular Reflex Evoked by High-Acceleration Rotations in the Squirrel Monkey. I. Normal Responses
Authors: Minor Lloyd B. , Lasker David M. , Backous Douglas D. , Hullar Timothy E.
Published: December 2017

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000°/s2 reaching a velocity of 150°/s) began after a latency of 7.3 ± 1.5 ms (mean ± SD). Gain of the reflex during the acceleration was 14.2 ± 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5–15 Hz with a peak velocity of 20°/s, the VOR gain measured 0.83 ± 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 ± 0.9° was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of ≥4 Hz (0.85 ± 0.04 at 4 Hz, 20°/s; 1.01 ± 0.05 at 100°/s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20°/s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.
Horizontal Vestibuloocular Reflex Evoked by High-Acceleration Rotations in the Squirrel Monkey. II. Responses After Canal Plugging
Authors: Lasker David M. , Backous Douglas D. , Lysakowski Anna , Davis Griffin L. , Minor Lloyd B.
Published: December 2017

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1–4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3,000°/s2, peak velocity = 150°/s) was 0.61 ± 0.14 (mean ± SD) for contralesional rotations and 0.33 ± 0.03 for ipsilesional rotations. Within 18–24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0.88 ± 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 ± 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 ± 0.4 ms for ipsilesional and 7.1 ± 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5–15 Hz, ±20°/s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies ≥4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 ± 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the linear pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonlinear pathway. This pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.
Mechanisms of Cannabinoid-Receptor–Mediated Inhibition of Synaptic Transmission in Cultured Hippocampal Pyramidal Neurons
Authors: Sullivan Jane M.
Published: December 2017

Cannabinoids, such as marijuana, are known to impair learning and memory perhaps through their actions in the hippocampus where cannabinoid receptors are expressed at high density. Although cannabinoid receptor activation decreases glutamatergic synaptic transmission in cultured hippocampal neurons, the mechanisms of this action are not known. Cannabinoid receptor activation also inhibits calcium channels that support neurotransmitter release in these cells, making modulation of these channels a candidate for cannabinoid-receptor–mediated effects on synaptic transmission. Whole cell patch-clamp recordings of glutamatergic neurons cultured from the CA1 and CA3 regions of the hippocampus were used to identify the mechanisms of the effects of cannabinoids on synaptic transmission. Cannabinoid receptor activation reduced excitatory postsynaptic current (EPSC) size by ∼50% but had no effect on the amplitude of spontaneous miniature EPSCs (mEPSCs). This reduction in EPSC size was accompanied by an increase in paired-pulse facilitation measured in low (1 mM) extracellular calcium and by a decrease in paired-pulse depression measured in normal (2.5 mM) extracellular calcium. Together, these results strongly support the hypothesis that cannabinoid receptor activation decreases EPSC size by reducing release of neurotransmitter presynaptically while having no effect on postsynaptic sensitivity to glutamate. Further experiments were done to identify the molecular mechanisms underlying this cannabinoid-receptor–mediated decrease in neurotransmitter release. Cannabinoid receptor activation had no effect on the size of the presynaptic pool of readily releasable neurotransmitter-filled vesicles, eliminating reduction in pool size as a mechanism for cannabinoid-receptor–mediated effects. After blockade of Q- and N-type calcium channels with ω-agatoxin TK and ω-conotoxin GVIA; however, activation of cannabinoid receptors reduced EPSC size by only 14%. These results indicate that cannabinoid receptor activation reduces the probability that neurotransmitter will be released in response to an action potential via an inhibition of presynaptic Q- and N-type calcium channels. This molecular mechanism most likely contributes to the impairment of learning and memory produced by cannabinoids and may participate in the analgesic, antiemetic, and anticonvulsive effects of these drugs as well.
Loss of I A Expression and Increased Excitability in Postnatal Rat Cajal-Retzius Cells
Authors: Mienville Jean-Marc , Maric Irina , Maric Dragan , Clay John R.
Published: December 2017

Although an important secretory function of Cajal-Retzius (CR) cells has been discovered recently, the precise electrical status of these cells among other layer I neurons in particular and in cortical function in general is still unclear. In this paper, early postnatal CR cells from rat neocortex were found to express an inactivating K current whose molecular substrate is likely to be the Kv1.4 channel. Both electrophysiological and immunocytochemical experiments revealed that expression of this A-type current is down-regulated in vivo and virtually disappears by the end of the second postnatal week. At this time, CR cells have become capable of evoked repetitive firing, and their action potentials are larger and faster, yet these electrical properties still appear incompatible with a role in cortical network function, as inferred from comparisons with other cortical neurons. Also at this time, a large proportion of CR cells display spontaneous spiking activity, which suggests the possibility of additional roles for these cells. We conclude that the loss of A channels along with an increase in Na channel density shape the changes in excitability of postnatal CR cells, in terms of both the patterns of evoked firing and the emergence of spontaneous spiking.
Large-Conductance Ca2+-Activated Potassium Channels in Secretory Neurons
Authors: Lara Jesús , Acevedo Juan José , Onetti Carlos G.
Published: December 2017

Large-conductance Ca2+-activated K+ channels (BK) are believed to underlie interburst intervals and contribute to the control of hormone release in several secretory cells. In crustacean neurosecretory cells, Ca2+entry associated with electrical activity could act as a modulator of membrane K+ conductance. Therefore we studied the contribution of BK channels to the macroscopic outward current in the X-organ of crayfish, and their participation in electrophysiological activity, as well as their sensitivity toward intracellular Ca2+, ATP, and voltage, by using the patch-clamp technique. The BK channels had a conductance of 223 pS and rectified inwardly in symmetrical K+. These channels were highly selective to K+ ions; potassium permeability ( P K) value was 2.3 × 10−13 cm3 s−1. The BK channels were sensitive to internal Ca2+ concentration, voltage dependent, and activated by intracellular MgATP. Voltage sensitivity ( k) was ∼13 mV, and the half-activation membrane potentials depended on the internal Ca2+ concentration. Calcium ions (0.3–3 μM) applied to the internal membrane surface caused an enhancement of the channel activity. This activation of BK channels by internal calcium had a K D(0) of 0.22 μM and was probably due to the binding of only one or two Ca2+ ions to the channel. Addition of MgATP (0.01–3 mM) to the internal solution increased steady state-open probability. The dissociation constant for MgATP ( K D) was 119 μM, and the Hill coefficient ( h) was 0.6, according to the Hill analysis. Ca2+-activated K+ currents recorded from whole cells were suppressed by either adding Cd2+ (0.4 mM) or removing Ca2+ ions from the external solution. TEA (1 mM) or charybdotoxin (100 nM) blocked these currents. Our results showed that both BK and KATP channels are present in the same cell. Even when BK and KATPchannels were voltage dependent and modulated by internal Ca2+ and ATP, the profile of sensitivity was quite different for each kind of channel. It is tempting to suggest that BK and KATP channels contribute independently to the regulation of spontaneous discharge patterns in crayfish neurosecretory cells.
Response of Inferior Colliculus Neurons to Electrical Stimulation of the Auditory Nerve in Neonatally Deafened Cats
Authors: Shepherd Robert K. , Baxi Jagir H. , Hardie Natalie A.
Published: December 2017

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1–2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 μs/phase biphasic current pulses. Single-unit ( n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10–25 ms) compared with those in the ICC (5–8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.
Role of GABAA and GABAC Receptors in the Biphasic GABA Responses in Neurons of the Rat Major Pelvic Ganglia
Authors: Akasu Takashi , Munakata Yoshikazu , Tsurusaki Masashi , Hasuo Hiroshi
Published: December 2017

The role of γ-aminobutyric acid-A (GABAA) and GABAC receptors in the GABA-induced biphasic response in neurons of the rat major pelvic ganglia (MPG) were examined in vitro. Application of GABA (100 μM) to MPG neurons produced a biphasic response, an initial depolarization (GABAd) followed by a hyperpolarization (GABAh). The input resistance of the MPG neurons was decreased during the GABAd, whereas it was increased during the GABAh. The GABAd could be further separated into the early component (early GABAd) with a duration of 27 ± 5 s (mean ± SE; n = 11) and the late component (late GABAd) with a duration of 109 ± 11 s ( n = 11). The duration of the GABAh was 516 ± 64 s ( n = 11). The effects of GABA (5–500 μM) in producing the depolarization and the hyperpolarization were concentration-dependent. GABA (5–30 μM) induced only late depolarizations. The early component of the depolarization appeared when the concentration of GABA was >50 μM. Muscimol produced only early depolarizing responses. Baclofen (100 μM) had no effect on the membrane potential and input resistance of MPG neurons. Bicuculline (60 μM) blocked the early GABAdbut not the late GABAd and the GABAh. Application of picrotoxin (100 μM) with bicuculline (60 μM) blocked both the late GABAd and the GABAh. CGP55845A (3 μM), a selective GABAB receptor antagonist, did not affect the GABA-induced responses. cis-4-Aminocrotonic acid (CACA, 1 mM) and trans-4-aminocrotonic acid (TACA, 1 mM), selective GABAC receptor agonists, produced late biphasic responses in the MPG neurons. The duration of the CACA responses was almost the same as those of the late GABAdand GABAh obtained in the presence of bicuculline. Imidazole-4-acetic acid (I4AA, 100 μM), a GABAC receptor antagonist, depressed the late GABAd and the GABAh but not the early GABAd. I4AA (100 μM) and picrotoxin (100 μM) also suppressed the biphasic response to CACA. The early GABAd and the late GABAd were reversed in polarity at −32 ± 3 mV ( n = 7) and −38 ± 2 mV ( n = 4), respectively, in the Krebs solution. The reversal potential of the GABAh was −34 ± 2 mV ( n = 4) in the Krebs solution. The reversal potentials of the late GABAd and the GABAh shifted to −20 ± 3 mV ( n = 5) and −22 ± 3 mV ( n = 5), respectively, in 85 mM Cl− solution. These results indicate that the late GABAd and the GABAh are mediated predominantly by bicuculline-insensitive, picrotoxin-sensitive GABA receptors, GABAC (or GABAAOr) receptors, in neurons of the rat MPG.
Quantal Unit Populations at theDrosophilaLarval Neuromuscular Junction
Authors: Wong K. , Karunanithi S. , Atwood H. L.
Published: December 2017

Focal extracellular recording at visualized boutons of the Drosophila larval neuromuscular junction was used to determine frequency and time course of the spontaneously occurring quantal events. When simultaneous intracellular recordings from the innervated muscle cell were made, more than one class of quantal event occurred at some of the individual boutons. “True” signals (arising at the bouton within the focal macropatch electrode) were often contaminated by additional signals generated outside the lumen of the focal electrode. Inclusion of these contaminating signals gave spuriously low values for relative amplitude, and spuriously high values for spontaneous quantal emission, for the synapses within the focal electrode. The contaminating signals, which appeared to be conducted along the subsynaptic reticulum surrounding the nerve terminals, generally were characterized by relatively small extracellular signals associated with normal intracellular events in the muscle fiber. From plots of simultaneous extracellular and intracellular recordings, the individual data points were classified according to the angles they subtended with the x axis (extracellular signal axis). Statistical procedures were developed to separate the true signals and contaminants with a high level of confidence. Populations of quantal events were found to be well described by Gaussian mixtures of two or three components, one of which could be characterized as the true signal population. Separation of signals from contaminants provides a basis for improving the estimates of quantal size and spontaneous frequency for the synapses sampled by the focal extracellular electrode.
Processing of Sound Sequences in Macaque Auditory Cortex: Response Enhancement
Authors: Brosch Michael , Schulz Andreas , Scheich Henning
Published: December 2017

It is well established that the tone-evoked response of neurons in auditory cortex can be attenuated if another tone is presented several hundred milliseconds before. The present study explores in detail a complementary phenomenon in which the tone-evoked response is enhanced by a preceding tone. Action potentials from multiunit groups and single units were recorded from primary and caudomedial auditory cortical fields in lightly anesthetized macaque monkeys. Stimuli were two suprathreshold tones of 100-ms duration, presented in succession. The frequency of the first tone and the stimulus onset asynchrony (SOA) between the two tones were varied systematically, whereas the second tone was fixed. Compared with presenting the second tone in isolation, the response to the second tone was enhanced significantly when it was preceded by the first tone. This was observed in 87 of 130 multiunit groups and in 29 of 69 single units with no obvious difference between different auditory fields. Response enhancement occurred for a wide range of SOA (110–329 ms) and for a wide range of frequencies of the first tone. Most of the first tones that enhanced the response to the second tone evoked responses themselves. The stimulus, which on average produced maximal enhancement, was a pair with a SOA of 120 ms and with a frequency separation of about one octave. The frequency/SOA combinations that induced response enhancement were mostly different from the ones that induced response attenuation. Results suggest that response enhancement, in addition to response attenuation, provides a basic neural mechanism involved in the cortical processing of the temporal structure of sounds.
Fast BK-Type Channel Mediates the Ca2+-Activated K+Current in Crayfish Muscle
Authors: Araque Alfonso , Buño Washington
Published: December 2017

The role of the Ca2+-activated K+current ( IK(Ca)) in crayfish opener muscle fibers is functionally important because it regulates the graded electrical activity that is characteristic of these fibers. Using the cell-attached and inside-out configurations of the patch-clamp technique, we found three different classes of channels with properties that matched those expected of the three different ionic channels mediating the depolarization-activated macroscopic currents previously described (Ca2+, K+, and Ca2+-dependent K+currents). We investigated the properties of the ionic channels mediating the extremely fast activating and persistent IK(Ca). These voltage- and Ca2+-activated channels had a mean single-channel conductance of ∼ 70 pS and showed a very fast activation. Both the single-channel open probability and the speed of activation increased with depolarization. Both parameters also increased in inside-out patches, i.e., in high Ca2+concentration. Intracellular loading with the Ca2+chelator bis(2-aminophenoxy) ethane- N, N,N′,N′-tetraacetic acid gradually reduced and eventually prevented channel openings. The channels opened at very brief delays after the pulse depolarization onset (<5 ms), and the time-dependent open probability was constant during sustained depolarization (≤560 ms), matching both the extremely fast activation kinetics and the persistent nature of the macroscopic IK(Ca). However, the intrinsic properties of these single channels do not account for the partial apparent inactivation of the macroscopic IK(Ca), which probably reflects temporal Ca2+variations in the whole muscle fiber. We conclude that the channels mediating IK(Ca)in crayfish muscle are voltage- and Ca2+-gated BK channels with relatively small conductance. The intrinsic properties of these channels allow them to act as precise Ca2+sensors that supply the exact feedback current needed to control the graded electrical activity and therefore the contraction of opener muscle fibers.