bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Types of Depolarization-Activated Potassium Currents in Acutely Isolated Mouse Vestibular Neurons
Authors: Chabbert C. , Chambard J. M. , Sans A. , Desmadryl G.
Published: December 2017

The nature and electrophysiological properties of Ca2+-independent depolarization-activated potassium currents were investigated in vestibular primary neurons acutely isolated from postnatal mice using the whole cell configuration of the patch-clamp technique. Three types of currents were identified. The first current, sensitive to TEA ( ITEA) and insensitive to 4-aminopyridine (4-AP), activated at −40 mV and exhibited slow activation ( τac, 38.4 ± 7.8 ms at −30 mV, mean ± SD). ITEAhad a half activation potential [ Vac(1/2)] of −14.5 ± 2.6 mV and was inactivated by up to 84.5 ± 5.7% by 10-s conditioning prepulses with a half inactivation potential [ Vinac(1/2)] of −62.4 ± 0.2 mV. The second current, sensitive to 4-AP (maximum block around 0.5 mM) and to α-dendrotoxin ( IDTX) appeared at −60 mV. Complete block of IDTXwas achieved using either 20 nM α-DTX or 50 nM margatoxin. This current activated 10 times faster than ITEA( τac, 3.5 ± 0.8 ms at −50 mV) with Vac(1/2)of −51.2 ± 0.6 mV, and inactivated only slightly compared with ITEA(maximum inactivation, 19.7 ± 3.2%). The third current, also sensitive to 4-AP (maximum block at 2 mM), was selectively blocked by application of blood depressing substance (BDS-I; maximum block at 250 nM). The BDS-I–sensitive current ( IBDS-I) activated around −60 mV. It displayed fast activation ( τac, 2.3 ± 0.4 ms at −50 mV) and fast and complete voltage-dependent inactivation. IBDS-Ihad a Vac(1/2)of −31.3 ± 0.4 mV and Vinac(1/2)of −65.8 ± 0.3 mV. It displayed faster time-dependent inactivation and recovery from inactivation than ITEA. The three types of current were found in all the neurons investigated. Although ITEAwas the major current, the proportion of IDTXand IBDS-Ivaried considerably between neurons. The ratio of the density of IBDS-Ito that of IDTXranged from 0.02 to 2.90 without correlation with the cell capacitances. In conclusion, vestibular primary neurons differ by the proportion rather than the type of the depolarization-activated potassium currents they express.
Surface Orientation Discrimination Activates Caudal and Anterior Intraparietal Sulcus in Humans: An Event-Related fMRI Study
Authors: Shikata Elisa , Hamzei Farsin , Glauche Volkmar , Knab René , Dettmers Christian , Weiller Cornelius , Büchel Christian
Published: December 2017

Perception of surface orientation is an essential step for the reconstruction of the three-dimensional (3D) structure of an object. Human lesion and functional neuroimaging studies have demonstrated the importance of the parietal lobe in this task. In primate single-unit studies, neurons in the caudal part of the intraparietal sulcus (CIP) were found to be active during the extraction of surface orientation through monocular (two-dimensional) cues such as texture gradients and linear perspective as well as binocular (3D) cues such as disparity gradient and orientation disparity. We used event-related fMRI to study the functional neuroanatomy of surface orientation discrimination using stimuli with monocular depth cues in six volunteers. Both posterior (CIP) and anterior (AIP) areas within the intraparietal sulcus showed a stronger activation during surface orientation as compared with a control (color discrimination) task using identical stimuli. Furthermore, the signal changes in CIP showed a greater performance effect than those in AIP, suggesting that CIP is tightly linked to the discrimination task.
Feedforward and Feedback Connections Between Areas V1 and V2 of the Monkey Have Similar Rapid Conduction Velocities
Authors: Girard P. , Hupé J. M. , Bullier J.
Published: December 2017

It is often assumed that the action of cortical feedback connections is slow and modulatory, whereas feedforward connections carry a rapid drive to their target neurons. Recent results from our laboratory showed a very rapid effect of feedback connections on the visual responses of neurons in lower order areas. We wanted to determine whether such a rapid action is mediated by fast conducting axons. Using electrical stimulation, we compared the conduction velocities along feedforward and feedback axons between areas V1 and V2 of the macaque monkey. We conclude that feedback and feedforward connections between V1 and V2 have comparable fast conduction velocities (around 3.5 m/s).
Venom From the Platypus,Ornithorhynchus anatinus,Induces a Calcium-Dependent Current in Cultured Dorsal Root Ganglion Cells
Authors: de Plater G. M. , Milburn P. J. , Martin R. L.
Published: December 2017

The platypus ( Ornithorhynchus anatinus), a uniquely Australian species, is one of the few living venomous mammals. Although envenomation of humans by many vertebrate and invertebrate species results in pain, this is often not the principal symptom of envenomation. However, platypus envenomation results in an immediate excruciating pain that develops into a very long-lasting hyperalgesia. We have previously shown that the venom contains a C-type natriuretic peptide that causes mast cell degranulation, and this probably contributes to the development of the painful response. Now we demonstrate that platypus venom has a potent action on putative nociceptors. Application of the venom to small to medium diameter dorsal root ganglion cells for 10 s resulted in an inward current lasting several minutes when the venom was diluted in buffer at pH 6.1 but not at pH 7.4. The venom itself has a pH of 6.3. The venom activated a current with a linear current-voltage relationship between −100 and −25 mV and with a reversal potential of −11 mV. Ion substitution experiments indicate that the current is a nonspecific cationic current. The response to the venom was blocked by the membrane-permeant Ca2+-ATPase inhibitor, thapsigargin, and by the tyrosine- and serine-kinase inhibitor, k252a. Thus the response appears to be dependent on calcium release from intracellular stores. The identity of the venom component(s) that is responsible for the responses we have described is yet to be determined but is probably not the C-type natriuretic peptide or the defensin-like peptides that are present in the venom.
Pretectal Neurons Optimized for the Detection of Saccade-Like Movements of the Visual Image
Authors: Price N.S.C. , Ibbotson M. R.
Published: December 2017

The visual response properties of nondirectional wide-field sensitive neurons in the wallaby pretectum are described. These neurons are called scintillation detectors (SD-neurons) because they respond vigorously to rapid, high contrast visual changes in any part of their receptive fields. SD-neurons are most densely located within a 1- to 2-mm radius from the nucleus of the optic tract, interspersed with direction-selective retinal slip cells. Receptive fields are monocular and cover large areas of the contralateral visual field (30–120°). Response sizes are equal for motion in all directions, and spontaneous activities are similar for all orientations of static sine-wave gratings. Response magnitude increases near linearly with increasing stimulus diameter and contrast. The mean response latency for wide-field, high-contrast motion stimulation was 43.4 ± 9.4 ms (mean ± SD, n = 28). The optimum visual stimuli for SD-neurons are wide-field, low spatial frequency (<0.2 cpd) scenes moving at high velocities (75–500°/s). These properties match the visual input during saccades, indicating optimal sensitivity to rapid eye movements. Cells respond to brightness increments and decrements, suggesting inputs from on and off channels. Stimulation with high-speed, low spatial frequency gratings produces oscillatory responses at the input temporal frequency. Conversely, high spatial frequency gratings give oscillations predominantly at the second harmonic of the temporal frequency. Contrast reversing sine-wave gratings elicit transient, phase-independent responses. These responses match the properties of Y retinal ganglion cells, suggesting that they provide inputs to SD-neurons. We discuss the possible role of SD-neurons in suppressing ocular following during saccades and in the blink or saccade-locked modulation of lateral geniculate nucleus activity to control retino-cortical information flow.
Gap Junctions and Inhibitory Synapses Modulate Inspiratory Motoneuron Synchronization
Authors: Bou-Flores Céline , Berger Albert J.
Published: December 2017

Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18α-glycyrrhetinic acid, 18β-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABAA and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal communication via gap junctions and inhibitory synaptic transmission.
Adaptive Adjustment of Connectivity in the Inferior Colliculus Revealed by Focal Pharmacological Inactivation
Authors: Gold Joshua I. , Knudsen Eric I.
Published: December 2017

In the midbrain sound localization pathway of the barn owl, a map of auditory space is synthesized in the external nucleus of the inferior colliculus (ICX) and transmitted to the optic tectum. Early auditory experience shapes these maps of auditory space in part by modifying the tuning of the constituent neurons for interaural time difference (ITD), a primary cue for sound-source azimuth. Here we show that these adaptive modifications in ITD tuning correspond to changes in the pattern of connectivity within the inferior colliculus. We raised owls with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. As reported previously, device rearing shifted the representation of ITD in the ICX and tectum but not in the primary source of input to the ICX, the central nucleus of the inferior colliculus (ICC). We applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to inactivate small populations of neurons that represented particular values of frequency and ITD. We measured the effect of this inactivation in the optic tecta of a normal owl and owls raised with the device. In the normal owl, inactivation at a critical site in the ICC eliminated responses in the tectum to the frequency-specific ITD value represented at the site of inactivation in the ICC. The location of this site was consistent with the known pattern of ICC-ICX-tectum connectivity. In the device-reared owls, adaptive changes in the representation of ITD in the tectum corresponded to dramatic and predictable changes in the locations of the critical sites of inactivation in the ICC. Given that the abnormal representation of ITD in the tectum depended on frequency and was likely conveyed directly from the ICX, these results suggest that experience causes large-scale, frequency-specific adjustments in the pattern of connectivity between the ICC and the ICX.
Extracellular Calcium Depletion as a Mechanism of Short-Term Synaptic Depression
Authors: King Richard D. , Wiest Michael C. , Montague P. Read
Published: December 2017

Recent experiments have demonstrated that normal neural activity can cause significant decrements in external calcium levels, and that these decrements mediate a form of short-term synaptic depression. These findings raise the possibility that certain forms of short-term synaptic depression at glutamatergic synapses throughout the mammalian CNS may be influenced by similar changes in external calcium. We use a computational model of the extracellular space, combined with experimental data on calcium consumption, to show that such short-term depression can be accounted for by changes in calcium just outside active synapses, provided that external calcium diffusion is restricted. Remarkably, the model suggests the novel possibility that synapses may possess private pools of external calcium that enforce some forms of short-term depression in a synapse-specific manner.
Muscarinic Depression of Synaptic Transmission in the Epileptogenic GABA Withdrawal Syndrome Focus
Authors: Silva-Barrat C. , Szente M. , Menini Ch. , Velluti J. C. , Champagnat J.
Published: December 2017

The GABA withdrawal syndrome (GWS) is a model of local status epilepticus consecutive to the interruption of a prolonged GABA infusion into the rat somatomotor cortex. Bursting patterns in slices from GWS rats include intrinsic bursts of action potentials (APs) induced by intracellular depolarizing current injection and/or paroxysmal depolarization shifts (PDSs) induced by white matter stimulation. Possible changes in the effects of cholinergic drugs after in vivo induction of GWS were investigated on bursting cells ( n = 30) intracellularly recorded in neocortical slices. In GWS slices, acetylcholine (Ach, 200-1000 μM) or carbachol (Cch, 50 μM) applications increased the number of bursts induced by depolarizing current injection while synaptically induced PDSs were significantly diminished (by 50–60%) or even blocked independently of the cholinergic-induced depolarization. The intrinsic burst facilitation and PDS depression provoked by Ach or Cch were mimicked by methyl-acetylcholine (mAch, 100–400 μM, n = 11), were reversed by atropine application (1–50 μM, n = 3), and were not mimicked by nicotine (50–100 μM, n = 4), indicating the involvement of muscarinic receptors. In contrast, in nonbursting cells from the same epileptic area ( n = 42) or from equivalent area in control rats ( n = 24), a nonsignificant muscarinic depression of EPSPs was induced by Cch and Ach. The mAch depression of excitatory postsynaptic potential (EPSPs) was significantly lower than that seen for PDSs in GWS rats. None of the cholinergic agonists caused bursting appearance in these cells. Therefore the present study demonstrates a unique implication of muscarinic receptors in exerting opposite effects on intrinsic membrane properties and on synaptic transmission in epileptiform GWS. Muscarinic receptor mechanisms may therefore have a protective role against the development and spread of epileptiform activity from the otherwise-activated epileptic focus.
Evidence for Interhemispheric Processing of Inputs From the Hands in Human S2 and PV
Authors: Disbrow Elizabeth , Roberts Tim , Poeppel David , Krubitzer Leah
Published: December 2017

In the present investigation, we identified cortical areas involved in the integration of bimanual inputs in human somatosensory cortex. Using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), we compared the responses to unilateral versus bilateral stimulation in anterior parietal cortex and areas in the Sylvian fissure of the contralateral hemisphere. The extent of fMRI activation on the upper bank of the Sylvian fissure, in the second somatosensory (S2) and the parietal ventral (PV) areas, was significantly larger for bilateral stimulation than for unilateral stimulation. Using MEG, we were able to describe the latency of response in S1 and S2/PV to unilateral and bilateral stimulation. The MEG response had three components under both stimulus conditions. An early peak in S1 at 40 ms, a middle peak in S2/PV at 80–160 ms, and three late peaks in S2/PV at 250–420 ms. There was an increase in magnetic field strength in S2/PV to bilateral stimulation at 300–400 ms post stimulus. The fMRI results indicate that, as in monkeys, S2/PV receives inputs from both the contralateral and ipsilateral hand. The MEG data suggest that information is processed serially from S1 to S2. The very late response in S2/PV indicates that extensive intrahemispheric processing occurs before information is transferred to the opposite hemisphere. The neural substrate for the increased activation and field strength at long latencies during bilateral stimulation can be accounted for in three ways. Under bilateral stimulus conditions, more neurons may be active, neuronal firing rate may increase, and/or neural activity may be more synchronous.
Group I mGluRs Coupled to G Proteins Are Regulated by Tyrosine Kinase in Dopamine Neurons of the Rat Midbrain
Authors: Tozzi Alessandro , Guatteo Ezia , Caputi Luigi , Bernardi Giorgio , Mercuri Nicola B.
Published: December 2017

Metabotropic glutamate receptors (mGluRs) modulate neuronal function via different transduction mechanisms that are either dependent or independent on G-protein function. Here we investigated, using whole cell patch-clamp recordings in combination with fluorimetric measurements of intracellular calcium concentration ([Ca2+]i), the metabolic pathways involved in the responses induced by group I mGluRs in dopamine neurons of the rat midbrain. The inward current and the [Ca2+]iincrease caused by the group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG, 100 μM) were permanently activated and subsequently abolished in cells loaded with the nonhydrolizable GTP-analogue GTP-γ-S (600 μM). In addition, when GDP-β-S (600 μM) was dialyzed into the cells to produce the blockade of the G proteins, the DHPG-dependent responses were reduced. When the tissue was bathed with the phospholipase C inhibitor 1-[6[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]exyl]-1H-pyrrole-2,5-dione (10 μM), the DHPG-induced calcium transients slightly diminished but the associated inward currents were not affected. Interestingly, a substantial depression of the DHPG-induced inward current and transient increase of [Ca2+]iwas caused by the protein tyrosine kinase inhibitors tyrphostin B52 (40 μM) and 4′,5,7-trihydroxyisoflavone (genistein; 40 μM), whereas genistein's inactive analogue 4′,5,7-trihydroxyisoflavone-7-glucoside (40 μM) was ineffective. The blockade of the Src family of tyrosine kinase by 4-amino-5-(4-methylphenyl)-7-( t-butyl)pyrazolo[3,4-d]pyrimidine (20 μM), mitogen-activated protein kinase by 2′-amino-3′ methoxyflavone (50 μM), and protein kinase C by staurosporine (1 μM) had no effect on the cellular responses caused by DHPG. The mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)-pyridine (10–100 μM) did not affect the actions of DHPG. Thus our results indicate that the responses, mainly mediated by mGluRs1 in dopamine neurons, are activated by intracellular mechanisms coupled to G proteins and regulated by tyrosine kinases.
Comparison of the Effect of Intrathecal Administration of Clonidine and Yohimbine on the Locomotion of Intact and Spinal Cats
Authors: Giroux Nathalie , Reader Tomás A. , Rossignol Serge
Published: December 2017

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate “fictive” locomotion in immobilized acutely spinalized cats and α2-noradrenergic agonists, such as 2,6,-dichloro- N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the α2 agonist, clonidine, and the antagonist (16α, 17α)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L3–L4before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50–150 μg/100 μl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800–1600 μg/100 μl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 μg/100 μl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.
Differential Fronto-Parietal Activation Depending on Force Used in a Precision Grip Task: An fMRI Study
Authors: Ehrsson H. Henrik , Fagergren Anders , Forssberg Hans
Published: December 2017

Recent functional magnetic resonance imaging (fMRI) studies suggest that the control of fingertip forces between the index finger and the thumb (precision grips) is dependent on bilateral frontal and parietal regions in addition to the primary motor cortex contralateral to the grasping hand. Here we use fMRI to examine the hypothesis that some of the areas of the brain associated with precision grips are more strongly engaged when subjects generate small grip forces than when they employ large grip forces. Subjects grasped a stationary object using a precision grip and employed a small force (3.8 N) that was representative of the forces that are typically used when manipulating small objects with precision grips in everyday situations or a large force (16.6 N) that represents a somewhat excessive force compared with normal everyday usage. Both force conditions involved the generation of time-variant static and dynamic grip forces under isometric conditions guided by auditory and tactile cues. The main finding was that we observed stronger activity in the bilateral cortex lining the inferior part of the precentral sulcus (area 44/ventral premotor cortex), the rostral cingulate motor area, and the right intraparietal cortex when subjects applied a small force in comparison to when they generated a larger force. This observation suggests that secondary sensorimotor related areas in the frontal and parietal lobes play an important role in the control of fine precision grip forces in the range typically used for the manipulation of small objects.
Effects of Acetylcholine and Atropine on Plasticity of Central Auditory Neurons Caused by Conditioning in Bats
Authors: Ji Weiqing , Gao Enquan , Suga Nobuo
Published: December 2017

In the big brown bat ( Eptesicus fuscus), conditioning with acoustic stimuli followed by electric leg-stimulation causes shifts in frequency-tuning curves and best frequencies (hereafter BF shifts) of collicular and cortical neurons, i.e., reorganization of the cochleotopic (frequency) maps in the inferior colliculus (IC) and auditory cortex (AC). The collicular BF shift recovers 180 min after the conditioning, but the cortical BF shift lasts longer than 26 h. The collicular BF shift is not caused by conditioning, as the AC is inactivated during conditioning. Therefore it has been concluded that the collicular BF shift is caused by the corticofugal auditory system. The collicular and cortical BF shifts both are not caused by conditioning as the somatosensory cortex is inactivated during conditioning. Therefore it has been hypothesized that the cortical BF shift is mostly caused by both the subcortical (e.g., collicular) BF shift and the activity of nonauditory systems such as the somatosensory cortex excited by an unconditioned leg-stimulation and the cholinergic basal forebrain. The main aims of our present studies are to examine whether acetylcholine (ACh) applied to the AC augments the collicular and cortical BF shifts caused by the conditioning and whether atropine applied to the AC abolishes the cortical BF shift but not the collicular BF shift, as expected from the preceding hypothesis. In the awake bat, we made the following findings. ACh applied to the AC augments not only the cortical BF shift but also the collicular BF shift through the corticofugal system. Atropine applied to the AC reduces the collicular BF shift and abolishes the cortical BF shift which otherwise would be caused. ACh applied to the IC significantly augments the collicular BF shift but affects the cortical BF shift only slightly. ACh makes the cortical BF shift long-lasting beyond 4 h, but it cannot make the collicular BF shift long-lasting beyond 3 h. Atropine applied to the IC abolishes the collicular BF shift. It reduces the cortical BF shift but does not abolish it. Our findings favor the hypothesis that the BF shifts evoked by the corticofugal system, and an increased ACh level in the AC evoked by the basal forebrain are both necessary to evoke a long-lasting cortical BF shift.
Sensory Input Directs Spatial and Temporal Plasticity in Primary Auditory Cortex
Authors: Kilgard Michael P. , Pandya Pritesh K. , Vazquez Jessica , Gehi Anil , Schreiner Christoph E. , Merzenich Michael M.
Published: December 2017

The cortical representation of the sensory environment is continuously modified by experience. Changes in spatial (receptive field) and temporal response properties of cortical neurons underlie many forms of natural learning. The scale and direction of these changes appear to be determined by specific features of the behavioral tasks that evoke cortical plasticity. The neural mechanisms responsible for this differential plasticity remain unclear partly because important sensory and cognitive parameters differ among these tasks. In this report, we demonstrate that differential sensory experience directs differential plasticity using a single paradigm that eliminates the task-specific variables that have confounded direct comparison of previous studies. Electrical activation of the basal forebrain (BF) was used to gate cortical plasticity mechanisms. The auditory stimulus paired with BF stimulation was systematically varied to determine how several basic features of the sensory input direct plasticity in primary auditory cortex (A1) of adult rats. The distributed cortical response was reconstructed from a dense sampling of A1 neurons after 4 wk of BF-sound pairing. We have previously used this method to show that when a tone is paired with BF activation, the region of the cortical map responding to that tone frequency is specifically expanded. In this report, we demonstrate that receptive-field size is determined by features of the stimulus paired with BF activation. Specifically, receptive fields were narrowed or broadened as a systematic function of both carrier-frequency variability and the temporal modulation rate of paired acoustic stimuli. For example, the mean bandwidth of A1 neurons was increased (+60%) after pairing BF stimulation with a rapid train of tones and decreased (−25%) after pairing unmodulated tones of different frequencies. These effects are consistent with previous reports of receptive-field plasticity evoked by natural learning. The maximum cortical following rate and minimum response latency were also modified as a function of stimulus modulation rate and carrier-frequency variability. The cortical response to a rapid train of tones was nearly doubled if BF stimulation was paired with rapid trains of random carrier frequency, while no following rate plasticity was observed if a single carrier frequency was used. Finally, we observed significant increases in response strength and total area of functionally defined A1 following BF activation paired with certain classes of stimuli and not others. These results indicate that the degree and direction of cortical plasticity of temporal and receptive-field selectivity are specified by the structure and schedule of inputs that co-occur with basal forebrain activation and suggest that the rules of cortical plasticity do not operate on each elemental stimulus feature independently of others.
Imaging of 4-AP–Induced, GABAA-Dependent Spontaneous Synchronized Activity Mediated by the Hippocampal Interneuron Network
Authors: Sinha Saurabh R. , Saggau Peter
Published: December 2017

Under conditions of increased excitability, such as application of the K+channel blocker 4-aminopyridine (4-AP, 100 μM), interneurons in the hippocampal slice show an additional form of synchronized activity that is distinct from the ictal and interictal epileptiform activity induced by these manipulations. In principal neurons, i.e., pyramidal and granule cells, this synchronized interneuron activity (SIA) generates large, multi-component synaptic potentials, which have been termed long-lasting depolarizations (LLDs). These LLDs are dependent on GABAA receptor-mediated synaptic transmission but not on excitatory amino acid (EAA) receptors. Intracellular recordings from hilar interneurons have shown that depolarizing GABAA receptor-mediated synaptic potentials are also largely responsible for the synchronization of interneurons. The spatiotemporal characteristics of this interneuron activity have not been investigated previously. Using a voltage-sensitive dye and optical techniques that are capable of recording spontaneous synchronized activity, we have characterized the spatiotemporal pattern of SIA (in the presence of 4-AP + EAA receptor antagonists) and compared it with interictal epileptiform activity (in 4-AP only). Like interictal activity, SIA could be observed throughout the hippocampal slice. Unlike interictal activity, which originated in area CA2/CA3 and spread from there, SIA was most prominent in area CA1 and originated either there or in the subiculum. In CA1, interictal activity was largest in and near stratum pyramidale , while SIA was mainly located in s. lacunosum moleculare. Furthermore SIA was equally likely to propagate in either direction, and multiple patterns of propagation could be observed within a single brain slice. These studies suggest that hippocampal area CA1 has the highest propensity for SIA, that multiple locations can serve as the site of origin, and that interneurons located in s. lacunosum moleculare or interneurons that specifically project to this region may be particularly important for synchronized interneuron activity.
Dendritic Calcium Spikes in Layer 5 Pyramidal Neurons Amplify and Limit Transmission of Ligand-Gated Dendritic Current to Soma
Authors: Oakley J. C. , Schwindt P. C. , Crill W. E.
Published: December 2017

Long-lasting, dendritic, Ca2+-dependent action potentials (plateaus) were investigated in layer 5 pyramidal neurons from rat neocortical slices visualized by infrared-differential interference contrast microscopy to understand the role of dendritic Ca2+ spikes in the integration of synaptic input. Focal glutamate iontophoresis on visualized dendrites caused soma firing rate to increase linearly with iontophoretic current until dendritic Ca2+ responses caused a jump in firing rate. Increases in iontophoretic current caused no further increase in somatic firing rate. This limitation of firing rate resulted from the inability of increased glutamate to change evoked plateau amplitude. Similar nonlinear patterns of soma firing were evoked by focal iontophoresis on the distal apical, oblique, and basal dendrites, whereas iontophoresis on the soma and proximal apical dendrite only evoked a linear increase in firing rate as a function of iontophoretic current without plateaus. Plateau amplitude recorded in the soma decreased as the site of iontophoresis was moved farther from the soma, consistent with decremental propagation of the plateau to the soma. Currents arriving at the soma summed if plateaus were evoked on separate dendrites or if subthreshold responses were evoked from sites on the same dendrite. If plateaus were evoked at two sites on the same dendrite, only the proximal plateau was seen at the soma. Just-subthreshold depolarizations at two sites on the same dendrite could sum to evoke a plateau at the proximal site. We conclude that the plateaus prevent current from ligand-gated channels distal to the plateau-generating region from reaching the soma and directly influencing firing rate. The implications of plateau properties for synaptic integration are discussed.
Long-Term Recordings of Networks of Immortalized GnRH Neurons Reveal Episodic Patterns of Electrical Activity
Authors: Nunemaker Craig S. , DeFazio R. Anthony , Geusz Michael E. , Herzog Erik D. , Pitts Gilbert R. , Moenter Suzanne M.
Published: December 2017

The CNS controls reproduction through pulsatile secretion of gonadotropin-releasing hormone (GnRH). Episodic increases in the firing rate of unidentified hypothalamic neurons have been associated with downstream markers of GnRH secretion. Whether this episodic electrical activity is intrinsic to GnRH neurons, intrinsic to other “pulse generator” neurons that drive GnRH neurons, or a combination of these is unknown. To determine if GnRH neurons display episodic firing patterns in isolation from other cell types, immortalized GnRH neurons (GT1-7 cells) were cultured on multiple microelectrode arrays. Long-term, multi-site recordings of GT1-7 cells revealed repeated episodes of increased firing rate with an interval of 24.8 ± 1.3 (SE) min that were completely eliminated by tetrodotoxin, a sodium channel blocker. This pattern was comprised of active units that fired independently as well as coincidentally, suggesting the overall pattern of electrical activity in GT1-7 cells emerges as a network property. The A-type potassium-channel antagonist 4-aminopyridine (1 mM) increased both firing rate and GnRH secretion, demonstrating the presence of A-type currents in these cells and supporting the hypothesis that electrical activity is associated with GnRH release. Physiologically relevant episodic firing patterns are thus an intrinsic property of immortalized GnRH neurons and appear to be associated with secretion. The finding that overall activity is derived from the sum of multiple independent active units within a network may have important implications for the genesis of the GnRH secretory pattern that is delivered to the target organ. Specifically, these data suggest not every GnRH neuron participates in each secretory pulse and provide a possible mechanism for the variations in GnRH-pulse amplitude observed in vivo.
Multiple Effects of Dopamine on Layer V Pyramidal Cell Excitability in Rat Prefrontal Cortex
Authors: Gulledge Allan T. , Jaffe David B.
Published: December 2017

The mechanisms underlying the inhibitory effects of dopamine (DA) on layer V pyramidal neuron excitability in the prelimbic region of the rat medial prefrontal cortex were investigated. Under control conditions, DA depressed both action potential generation (driven by somatic current injection) and input resistance ( R N). The presence of GABAA receptor antagonists blocked DA-induced depression of action potential generation and revealed a delayed increase in excitability that persisted for the duration of experimental recording, up to 20 min following the washout of DA. In contrast to spike generation, disinhibition did not affect the transient depression of R N produced by DA, suggesting independent actions of DA on spike generation and R N. Consistent with the hypothesis that DA acts to decrease pyramidal cell output via a GABAergic mechanism, DA increased the frequency of spontaneous inhibitory postsynaptic currents in both the absence and presence of TTX. Furthermore focal application of GABA to a perisomatic region mimicked the inhibitory effect of DA on spike production without affecting R N. Focal application of bicuculline to the same location reversed the inhibitory effect of bath-applied DA on spike generation, while again having no effect on R N. The depression of R N by DA was both occluded and mimicked by the Na+ channel blocker TTX, suggesting the involvement of a Na+ conductance in reducing pyramidal cell R Nduring the acute presence of DA. Together these data demonstrate that the acute presence of DA decreases pyramidal neuron excitability by two independent mechanisms. At the same time DA triggers a delayed and longer-lasting increase in excitability that is partially masked by synaptic inhibition.
Preserving and Restoring Behavioral Potential Within the Spinal Cord Using an Instrumental Training Paradigm
Authors: Crown Eric D. , Grau James W.
Published: December 2017

We have shown that spinal cord neurons can support a simple form of instrumental learning. In a typical experiment, rats are spinalized at the second thoracic vertebra (T2) and given shock to one hindleg. One group (master) receives shock whenever the leg is extended. This response-contingent shock causes an increase in response duration that decreases net shock exposure. This instrumental learning is not observed in yoked controls that receive the same amount of shock independent of leg position (noncontingent shock). Interestingly, rats that have received noncontingent shock also fail to learn when they are subsequently exposed to response-contingent shock on either the ipsilateral or contralateral leg. Just 6 min of noncontingent nociceptive stimulation, applied to the leg or tail, undermines behavioral potential for up to 48 h. The present experiments explore whether a behavioral therapy can prevent and/or reverse this deficit. In experiment 1, spinalized rats received 30 min of training with contingent shock, noncontingent shock, or nothing prior to noncontingent tailshock. They were then tested with contingent shock to the contralateral hindleg. Rats that had received noncontingent shock alone failed to learn. Prior exposure to contingent shock had an immunizing effect that prevented the deficit. Experiment 2examined whether training with contingent shock after noncontingent shock exposure would restore behavioral potential. To facilitate performance during contingent shock training, subjects were given an intrathecal injection of the opioid antagonist naltrexone, a drug treatment that temporarily blocks the expression of the behavioral deficit. Twenty-four hours later subjects were tested with contingent shock on either the ipsilateral or contralateral leg. We found that naltrexone combined with contingent shock therapy restored spinal cord function. Naltrexone alone had no effect. The results suggest that noncontingent nociceptive stimulation can undermine behavioral potential after spinal cord injury and that instrumental training can help preserve, and protect, spinal cord function.
Motion Information Is Spatially Localized in a Visual Working-Memory Task
Authors: Zaksas Daniel , Bisley James W. , Pasternak Tatiana
Published: December 2017

We asked if the information about stimulus motion used in a visual working-memory task is localized in space. Monkeys compared the directions of two moving random-dot stimuli, sample and test, separated by a temporal delay and reported whether the stimuli moved in the same or in different directions. By presenting the two comparison stimuli in separate locations in the visual field, we determined whether information about stimulus direction was spatially localized during the storage and retrieval/comparison components of the task. Two psychophysical measures of direction discrimination provided nearly identical estimates of the critical spatial separation between sample and test stimuli that lead to a loss in threshold. Direction range thresholds measured with dot stimuli consisting of a range of local directional vectors were affected by spatial separation when a random-motion mask was introduced during the delay into the location of the upcoming test. The selective masking at the test location suggests that the information about the remembered direction was localized and available at that location. Direction difference thresholds, measured with coherently moving random dots, were also affected by separation between the two comparison stimuli. The separation at which performance was affected in both tasks increased with retinal eccentricity in parallel with the increase in receptive-field size in neurons in cortical area MT. The loss with transfer of visual information between different spatial locations suggests a contribution of cortical areas with localized receptive fields to the performance of the memory task. The similarity in the spatial scale of the storage mechanism derived psychophysically and the receptive field size of neurons in area MT suggest that MT neurons are central to this task.
Effects of Auditory Stimulus Context on the Representation of Frequency in the Gerbil Inferior Colliculus
Authors: Malone B. J. , Semple M. N.
Published: December 2017

Prior studies of dynamic conditioning have focused on modulation of binaural localization cues, revealing that the responses of inferior colliculus (IC) neurons to particular values of interaural phase and level disparities depend critically on the context in which they occur. Here we show that monaural frequency transitions, which do not simulate azimuthal motion, also condition the responses of IC neurons. We characterized single-unit responses to two frequency transition stimuli: a glide stimulus comprising two tones linked by a linear frequency sweep (origin-sweep-target) and a step stimulus consisting of one tone followed immediately by another (origin-target). Using sets of glide and step stimuli converging on a common target, we constructed conditioned response functions (RFs) depicting the variability in the response to an identical stimulus as a function of the preceding origin frequency. For nearly all cells, the response to the target depended on the origin frequency, even for origins outside the excitatory frequency response area of the cell. Results from conditioned RFs based on long (2–4 s) and short (200 ms) duration step stimuli indicate that conditioning effects can be induced in the absence of the dynamic sweep, and by stimuli of relatively short duration. Because IC neurons are tuned to frequency, changes in the origin frequency often change the “effective” stimulus duty cycle. In many cases, the enhancement of the target response appeared related to the decrease in the “effective” stimulus duty cycle rather than to the prior presentation of a particular origin frequency. Although this implies that nonselective adaptive mechanisms are responsible for conditioned responses, slightly more than half of IC neurons in each paradigm responded significantly differently to targets following origins that elicited statistically indistinguishable responses. The prevailing influence of stimulus context when discharge history is controlled demonstrates that not all the mechanisms governing conditioning depend on the discharge history of the recorded neuron. Selective adaptation among the neuron's variously tuned afferents may help engender stimulus-specific conditioning. The demonstration that conditioning effects reflect sensitivity to spectral as well as spatial stimulus contrast has broad implications for the processing of a wide range of dynamic acoustic signals and sound sequences.
Voltage-Gated Sodium Channels Shape Subthreshold EPSPs in Layer 5 Pyramidal Neurons From Rat Prefrontal Cortex
Authors: González-Burgos Guillermo , Barrionuevo German
Published: December 2017

The role of voltage-dependent channels in shaping subthreshold excitatory postsynaptic potentials (EPSPs) in neocortical layer 5 pyramidal neurons from rat medial prefrontal cortex (PFC) was investigated using patch-clamp recordings from visually identified neurons in brain slices. Small-amplitude EPSPs evoked by stimulation of superficial layers were not affected by the N-methyl-d-aspartate receptor antagonistd-2-amino-5-phosphonopentanoic acid but were abolished by the AMPA receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione, suggesting that they were primarily mediated by AMPA receptors. AMPA receptor-mediated EPSPs (AMPA-EPSPs) evoked in the apical dendrites were markedly enhanced, or increased in peak and duration, at depolarized holding potentials. Enhancement of AMPA-EPSPs was reduced by loading the cells with lidocaine N-ethylbromide (QX-314) and by local application of the Na+ channel blocker tetrodotoxin (TTX) to the soma but not to the middle/proximal apical dendrite. In contrast, blockade of Ca2+ channels by co-application of Cd2+ and Ni2+ to the soma or apical dendrite did not affect the AMPA-EPSPs. Like single EPSPs, EPSP trains were shaped by Na+ but not Ca2+ channels. EPSPs simulated by injecting synaptic-like current into proximal/middle apical dendrite (simEPSPs) were enhanced at depolarized holding potentials similarly to AMPA-EPSPs. Extensive blockade of Ca2+ channels by bath application of the Cd2+ and Ni2+ mixture had no effects on simEPSPs, whereas bath-applied TTX removed the depolarization-dependent EPSP amplification. Inhibition of K+ currents by 4-aminopyridine (4-AP) and TEA increased the TTX-sensitive EPSP amplification. Moreover, strong inhibition of K+ currents by high concentrations of 4-AP and TEA revealed a contribution of Ca2+channels to EPSPs that, however, seemed to be dependent on Na+ channel activation. Our results indicate that in layer 5 pyramidal neurons from PFC, Na+, and K+ voltage-gated channels shape EPSPs within the voltage range that is subthreshold for somatic action potentials.