bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonazepam suppresses GABAB-mediated inhibition in thalamic relay neurons through effects in nucleus reticularis
Authors: Huguenard J. R. , Prince D. A.
Published: December 2017

1. Experiments were carried out using patch-clamp techniques in rat thalamic slices, maintained in vitro, to examine the effects of the benzodiazepine compound, clonazepam (CZP), on intrathalamic inhibition. Bath-applied CZP reduced the gamma-aminobutyric acid-B (GABAB) component of inhibitory postsynaptic potentials and currents (IPSPs and IPSCs, respectively) evoked in rat thalamic somatosensory relay neurons by stimulation of nucleus reticularis thalami (nRt), without consistently affecting the GABAA IPSP. Secondary IPSPs, which occur as a result of intrathalamic oscillations, were dramatically reduced. 2. Voltage-clamp experiments combined with local or bath perfusion of the GABAA antagonist bicuculline methiodide (BMI), demonstrated that nRt is a site of GABAA-mediated postsynaptic inhibition that affects inhibitory output onto relay neurons. BMI enhanced both GABAA and GABAB postsynaptic inhibition in relay neurons when applied to nRt. Focal applications in the ventrobasal relay nucleus near the recording electrode blocked the GABAA-mediated IPSP but had no effects on GABAB inhibitory potentials. 3. Results suggest that CZP acts to facilitate recurrent inhibition in nRt and decrease its inhibitory output onto relay neurons. Intra-nRt GABAA-mediated inhibition thus has an important role in controlling thalamic excitability and in the anti-absence actions of CZP.
Corrigenda for Wide-field nondirectional visual units in the pretectum: do they suppress ocular following of saccade-induced visual stimulation
Authors: Ibbotson M. R. , Mark R. F.
Published: December 2017

Pages 1448–1450: M. R. Ibbotson and R. F. Mark, “Wide-field nondirectional visual units in the pretectum: do they suppress ocular following of saccade-induced visual stimulation.” Page 1450, right column, preceding references, the following dates should be inserted: Received 6 April 1994; accepted in final form 10 May 1994.
Carbachol-induced synchronized rhythmic bursts in CA3 neurons of guinea pig hippocampus in vitro
Authors: Bianchi R. , Wong R. K.
Published: December 2017

1. Carbachol effects on CA3 hippocampal cells were studied in the absence of ionotropic glutamatergic and GABAergic transmission with intracellular and extracellular recordings from guinea pig septohippocampal slices. 2. In all experiments the perfusing solution contained ionotropic glutamate and gamma-aminobutyric acid (GABA) receptor blockers [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10–20 microM), 3-((+/-)-2-carboxypiperazin-4-il)propyl-1-phosphonic acid (CPP, 10–20 microM), and picrotoxin (50 microM), respectively]. Under these conditions, the excitatory and early inhibitory postsynaptic potentials, evoked in CA3 pyramidal cells by mossy fiber stimulation before the addition of the blockers, were completely suppressed. 3. Carbachol (50 microM) introduced via bath perfusion or pulse application elicited a series of rhythmic bursts with overriding action potentials. Each rhythmic burst lasted up to 30 s and repeated at intervals of 0.7–6 min. Rhythmic bursts were blocked by atropine (1 microM). 4. At membrane potentials more depolarized than -70 mV, carbachol also elicited a sustained depolarization associated with an increase in membrane input resistance and action-potential firing. This response was blocked by atropine (1 microM). 5. Carbachol can induce both rhythmic bursts and sustained depolarizations in the same cell. Rhythmic bursts were elicited when the membrane potential of the cell was more hyperpolarized than -70 mV; sustained depolarizing responses were activated by carbachol when the cell membrane potential was more depolarized than -70 mV. 6. Extracellular field potential responses in the CA3 region occurred simultaneously with rhythmic bursts, indicating the synchronization of the event in the CA3 field. Dual intracellular recordings confirmed that rhythmic bursts occurred simultaneously in CA3 hippocampal pyramidal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
The anatomic organization of evoked potentials in rat parietal cortex: electrically evoked commissural responses
Authors: Barth D. S. , Kithas J. , Di S.
Published: December 2017

1. Two 8 x 8 channel microelectrode arrays were positioned over 3.5 x 3.5 mm2 areas in homologous regions of right and left parietal cortex of four rats. Potentials were evoked by delivering epicortical electrical stimulation to each electrode on one hemisphere while mapping the commissural response from the contralateral array. Spatial distributions of the electrically evoked potential (EECP) complex were compared directly with cytochrome oxidase-stained sections of the recorded region. 2. Electrode sites most capable of eliciting a commissural EECP were arranged along a diagonal band extending medially from the rostral to caudal region of each electrode array, approximating the pattern of dysgranular cortex separating primary auditory (Te1) from primary somatosensory (Par1) cortex. Electrode sites in the rostromedial and caudolateral region were ineffectual in eliciting an EECP in either hemisphere. Stimulation sites within secondary visual cortex (Oc2L) also produced strong responses. Only weak responses were elicited from stimulation of Te1 and no EECP could be evoked when stimulating within Par1. 3. When an EECP in the maximally sensitive diagonal region was elicited, its spatial distribution was typically asymmetrical throughout the recording array; the response was largest along a diagonal region also extending medially from the rostral to caudal area of each electrode array. Thus the pattern of EECP in each hemisphere closely matched the pattern of electrically excitable regions in the contralateral hemisphere. 4. The EECP was usually heterogeneous. EECP distributions within the strongly responding diagonal area often formed two regions of maximum amplitude separated by a less active zone. Although responses in Te1 were significantly weaker than those in the adjacent dysgranular cortex, they also revealed a heterogeneous spatial distribution with multiple closely spaced maxima. Only responses in Oc2L appeared consistently homogeneous, with a single maximum representing the EECP. 5. These results provide functional evidence supporting a model of parietal cortex in which there are two basic types of recipient regions, densely granular regions, which are the termination sites of specific thalamocortical fibers, and dysgranular or agranular regions, which receive both ipsilateral and contralateral projections. The functional parceling of rodent parietal cortex on the basis of the spatial and temporal distribution of the epicortical evoked potential complex may be superimposed onto the anatomic parceling into granular and dysgranular zones. Implications for stages of sensory information processing are discussed.
Use of spike triggered averaging of muscle activity to quantify inputs to motoneuron pools
Authors: Fortier P. A.
Published: December 2017

1. The goal of this study was to determine the extent to which postspike facilitation (PSpF) of electromyograms (EMGs) could be used to estimate the inputs to separate motoneuron pools, under conditions where there was wide variability in the parameters of muscle activity. These parameters included cancellation of motor unit action potentials (MUAPs), variations in EMG noise, and changes in MUAP amplitude and duration. A systematic series of computer simulations with increasing complexity were used to achieve this goal. The initial simulations (model I) included a premotoneuronal (PreM) cell connected to a single postsynaptic motoneuron (Mn), which in turn projected to a muscle. The next simulations (model II) included other target motoneurons with their efferents each projecting to separate muscles. The last simulations (model III) included more than one postsynaptic motoneuron per Mn-pool, as is the case in mammalian neuromuscular systems. 2. A sample simulation (model I) was performed to determine if the PreM-evoked effects were within physiologically observed values. A cross-correlogram (XC) calculated from a PreM cell and its target Mn, receiving a PreM-evoked excitatory postsynaptic potential (EPSP) of 0.5 mV, produced a XC peak area of 0.04 Mn-spikes/PreM-trigger. The PSpF of EMG activity evoked by this PreM cell had a mean percent increase of 4.6% (MPI = mean bin amplitude of PSpF above baseline/mean baseline level x 100). These XC and PSpF values were within the range of values previously obtained from animal experiments. 3. The magnitude of MUAP cancellation in the EMG was tested by calculating two spike-triggered averages (SpTAs) of EMGs from Mn-triggers (not PreM-triggers as in the other SpTAs): one using typical bipolar MUAPs and another using their rectified counterpart of only positive polarity to eliminate the possibility of MUAP cancellation. The PSpF calculated from bipolar spikes was 24.8% smaller than the one calculated using unipolar spikes. This cancellation could be greater or smaller depending on the state of parameters, such as the shape and number of MUAPs, that determine the probability of overlap between MUAP components of opposite polarity. All subsequent computer simulations used typical bipolar MUAPs. 4. A series of increasing motoneuron EPSP amplitudes were used to determine the relationship between PreM-Mn connection strength and PSpF area. A nearly perfect linear relationship between EPSP amplitude and PSpF area was obtained for SpTAs of rectified EMGs (r = 0.99). An equally linear relationship was obtained when averaging nonrectified EMGs (r = 0.99), but the smaller EPSPs or weaker synaptic connections were not detected.(ABSTRACT TRUNCATED AT 400 WORDS)
The role of an inwardly rectifying chloride conductance in postsynaptic inhibition
Authors: Staley K.
Published: December 2017

1. The relationship of the activation of a voltage-sensitive chloride conductance [GCl(V)] to the chloride transmembrane equilibrium potential (ECl) and the consequent role of this conductance in determining the effect of the gamma-aminobutyric acid-A (GABAA) receptor-mediated transmembrane chloride (Cl-) flux were investigated with the use of whole-cell recordings in the CA1 and dentate gyrus regions of adult rat hippocampal slice preparations. 2. GCl(V) was inwardly rectifying, with significant conductance only at membrane potentials more negative than ECl. For all tested neuronal Cl- concentrations, the activation of GCl(V) could be described by a Boltzman equation with an average half-activation voltage 15 mV negative to ECl, a slope factor of 14 mV, and a maximum conductance of 5 microS. There was no time-dependent inactivation of GCl(V). 3. GCl(V) was modulated by intracellular divalent cations. When magnesium was omitted from the electrode solution, the inward rectification of GCl(V) was unchanged, but the maximum amplitude of GCl(V) increased by a factor of 1.7. GCl(V) was blocked by bath application of 100 microM zinc (Zn2+), but not when 1–6 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) were present in the electrode solution. 4. GCl(V) was increased by 10 microM norepinephrine, and by activation of protein kinase A (PKA) with 1 mM 8-bromoadenosine cyclic monophosphate (8-Br cAMP). GCl(V) was blocked by activation of protein kinase C (PKC) with 10 microM phorbol 12,13-dibutyrate (PdBu) or 1-oleoyl-2-acetyl-sn-glycerol (OAG). 5. GCl(V) was present in all tested CA1 pyramidal neurons but no dentate gyrus neurons. In standard extracellular solution, the amplitude of GCl(V) was initially negligible but increased with recording time, suggesting that under normal conditions GCl(V) is blocked by an endogenous divalent cation or downregulated by PKC. 6. In current-clamp recordings, the steady-state resting membrane potential (RMP) diminished with Cl- loading, from -73 mV (4 mM electrode Cl-) to -27 mV (131 mM electrode Cl-). When GCl(V) was blocked with PdBu, there was no change in the RMP with Cl- loading. When electroneutral Cl- transport was blocked, voltage-clamp experiments using electrode Cl- concentrations of 4–131 mM demonstrated that ECl changed in parallel with the holding potential, but not when GCl(V) was blocked by PdBu.(ABSTRACT TRUNCATED AT 400 WORDS)
Functional and anatomic organization of three-dimensional eye movements in rabbit cerebellar flocculus
Authors: Van der Steen J. , Simpson J. I. , Tan J.
Published: December 2017

1. The three -dimensional, binocular eye movements evoked by electrical microstimulation of the cerebellar flocculus of alert, pigmented rabbits were recorded using the scleral search coil technique. The components of these eye movements were obtained in reference to an orthogonal coordinate system consisting of a vertical axis and two horizontal axes at 45 degrees and 135 degrees azimuth. The azimuth coordinate was taken to increase to both sides from the 0 degrees reference in the direction of the nose. 2. Eye movements were evoked most readily by stimulation (0.2 -ms pulses at 200 Hz for 1 s, intensity < or = 20 microA) at loci in the deep granular layer and the white matter. They consisted of slow (5–20 deg/s) movements. The responses were either binocular, with the eye ipsilateral to the stimulated flocculus usually having the larger amplitude, or were monocular, in which case they were restricted to the ipsilateral eye. 3. The evoked responses were classified according to the combination of the largest measured component of rotation for the two eyes and its sense of rotation (clockwise, CW, or counterclockwise, CCW). Seventy -eight percent of the evoked eye movements could be placed in one of two classes. For one of these classes the largest response component was a short -latency abduction of the ipsilateral eye about its vertical axis (19%), whereas for the other class (59%), the largest response component was a short -latency CCW rotation of the ipsilateral (left) eye about its 135 degrees axis. This response was frequently (50%) accompanied by a smaller short -latency CW rotation of the contralateral (right) eye about its 45 degrees axis. 4. The two main classes of three -dimensional eye movements are associated differentially with anatomically distinguishable compartments that are revealed by acetylcholinesterase histochemistry. Of the five anatomically distinguishable compartments in the floccular white matter, three are predominant. The middle of these three compartments is associated with the vertical axis class of movements, whereas the two adjacent compartments are associated with the 135 degrees class of eye movements. The eye movement relation of the other two, smaller compartments, was not determined. 5. The spatial orientation of the rotation axes of the two main classes of evoked eye movements closely corresponds to that of the preferred axes of the visual climbing fiber input to the flocculus. This suggests that both are organized in a similar coordinate system.(ABSTRACT TRUNCATED AT 400 WORDS)
Body postural muscles active during food arousal in Aplysia are modulated by diverse neurons that receive monosynaptic excitation from the neuron C-PR
Authors: Nagahama T. , Weiss K. R. , Kupfermann I.
Published: December 2017

1. We previously found that identified neuron C -PR may mediate the appetitive feeding posture of Aplysia by actions on appropriate motor neurons and perhaps on modulatory neurons innervating the foot and neck. In the present experiments, we attempted to further investigate this hypothesis by characterizing the modulatory neurons that are excited by CP -R. 2. We identified three types of modulatory neurons all of which are excited, at least in part, by monosynaptic excitatory connections from C-PR. 3. The cell bodies of these neurons are located in the posterior region of the pedal ganglion. 4. The neurons send axons to muscles, but rather than producing contractions, they enhance, depress, or alter the relaxation rate of contractions produced by motor neurons. Each of these types of modulatory neurons produces a highly specific effect in terms of the region of the body affected and the nature of the modulation. 5. The primary effect of P1R-E neurons was to enhance longitudinal contractions of the anterior foot. 6. P1R-D neurons depressed longitudinal and transverse contractions of the anterior foot. 7. P8R neurons enhanced longitudinal and transverse contractions of the neck. 8. The results obtained from extracellular recordings of muscle junction potentials suggest that the firing of the modulatory neurons may enhance or depress muscle contractions, at least in part, by increasing or decreasing the size of the excitatory input the motor neurons produce on the appropriate muscles. These changes in excitatory drive to the muscle are likely to underlie, at least in part, the alterations in contraction size produced by the modulatory neurons, but changes in relaxation rate are likely related to other actions of the modulatory neurons. 9. We have evidence for at least nine neurons that modulate the foot or neck and are excited by C-PR, and it is very likely that there are more, perhaps considerably more, of these types of neurons. In fact, it appears as if a significant proportion of the efferent output to the muscles that mediate the appetitive phase of feeding consists of modulatory output rather than conventional motor neuron output that produces discreet contractions.
Paired-pulse facilitation in the dentate gyrus: a patch-clamp study in rat hippocampus in vitro
Authors: Andreasen M. , Hablitz J. J.
Published: December 2017

1. Whole-cell patch-clamp recordings were used to study paired-pulse facilitation (PPF) of the lateral perforant path input to the dentate gyrus in thin hippocampal slices. 2. Orthodromic stimulation of the lateral perforant pathway evoked a excitatory postsynaptic current (EPSC) with a latency of 3.3 +/- 0.1 ms (mean +/- SE) that fluctuated in amplitude. The EPSC had a rise time (10-90%) of 2.79 +/- 0.06 ms (n = 35) and decayed with a single exponential time course with a time-constant of 9.14 +/- 0.24 ms (n = 35). No correlation was found between the amplitude of the EPSC and the rise time or decay time-constant. The non-N-methyl-D-aspartate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione completely blocked the EPSC whereas the NMDA antagonist D-aminophosphonovaleric acid (APV) had modest effects. 3. When a test (T-)EPSC was preceded at an interval of 100 ms by a conditioning (C-)EPSC, a significant increase in the amplitude of the T-EPSC was seen in 38 out of 44 trials analyzed from a total of 27 granule cells. The average amount of PPF was 35.7 +/- 2.1%. There was no apparent correlation between the amount of PPF and the stimulation intensity or mean amplitude of the C-EPSC. The time course of the facilitated T-EPSC was not significantly different from that of the C-EPSC. 4. No correlation was found between the amplitude of the C-EPSC and that of the T-EPSC. Estimates of quantal content (mcv) were determined by calculating the ratio of the squared averaged EPSC amplitude (from 48 responses) to the variance of these responses (M2/sigma 2) whereas quantal amplitudes (qcv) were estimated by calculating the ratio of the response variance to average EPSC amplitude (sigma 2/M). PPF was found to be associated with an average increase in mcv of 64.8 +/- 7.2% (n = 38) whereas qcv was decreased by 12.1 +/- 3.8%. 5. The time course of PPF was studied by varying the interval between the C- and T-pulse from 10 to 400 ms while keeping the stimulation intensity constant. Maximal facilitation of the T-EPSC was obtained with interpulse intervals < or = 25 ms where the average facilitation amounted to approximately 70% (n = 6). The decline of facilitation was nearly exponential and was no longer evident with intervals > 350 ms.(ABSTRACT TRUNCATED AT 400 WORDS
Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels
Authors: Matzner O. , Devor M.
Published: December 2017

1. We used the tested fiber method to record from single myelinated afferents axons ending in a chronic nerve injury site (neuroma) in the rat sciatic nerve or L4,5 dorsal root. Axons were chosen for study that fired spontaneously with a stable tonic or interrupted (bursty) autorhythmic firing pattern. 2. Agents that block voltage-sensitive Na+ channels [tetrodotoxin (TTX), lidocaine], voltage-sensitive Ca2+ channels (Cd2+, Co2+, Ni2+, verapamil, D600, nifedipine, and fluarizine), volt-age-sensitive K+ channels [tetraethylammonium (TEA), 4-aminopyridine (4-AP)], and Ca(2+)-activated K+ channels (gK+Ca2+;quinidine, apamine) were applied topically to the neuroma. Effects on baseline rhythmogenesis and on the duty cycle of bursting were documented. Spike pattern analysis was used to determine whether changes in firing frequency were associated with changes in impulse initiation (electrogenesis), or resulted from (partial) block of impulse propagation downstream from the site of electrogenesis. Effects of veratridine were also noted. 3. Na+ channel blockers consistently quenched neuroma firing, and they did so by suppressing the process of impulse initiation. Only rarely was propagation block the dominant process. In bursty fibers the duration of on-periods shortened as the duration of off-periods lengthened, without a significant change in the baseline interspike interval (ISI). Veratridine accelerated firing, also via the impulse generating process. 4. Ca2+ channel blockers had essentially no effect on baseline firing rate (i.e., ISI). 5. Ca2+ channel blockers, as well as blockers of gK+Ca2+, had substantial, but inconsistent effects on burst pattern. It is not clear whether this reflects variability in the experimental conditions, or heterogeneity among the fibers sampled. 6. Blockade of K+ channels failed to evoke rhythmogenesis in acutely cut axons as it does in chronically injured axons, even in the presence of veratridine. This is consistent with other evidence that ectopic neuroma firing depends on postinjury remodeling of membrane electrical properties. 7. The data indicate that, in chronically injured axons, the inward currents that underly electrogenicity, enable ectopic discharge, and, together with outward K+ currents, set the fundamental firing rhythm (ISI), operate primarily with the use of voltage-sensitive Na+ rather than Ca2+ channels. 8. The on-off duty cycle in bursty fibers was affected by Na+ channel ligands and also, although less so, and less consistently by, Ca2+ channel ligands. This indicates that both may play a role in the slow modulations of membrane potential that presumably underly interrupted autorhythmicity.
Metabotropic glutamate receptor activation induces calcium waves within hippocampal dendrites
Authors: Jaffe D. B. , Brown T. H.
Published: December 2017

1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [Ca2+]i were visualized as changes in the fluorescence of the Ca(2+)-sensitive dye Fluo-3. 2. Brief application of the specific mGlu receptor agonist (1S,3R)-ACPD to either the apical or basal dendrites produced initially localized increases in [Ca2+]i that subsequently propagated as waves throughout much of the neuron. These Ca2+ waves, which propagated at approximately 40 microns/s, were shown not to reflect intracellular Ca2+ diffusion or extracellular diffusion of ACPD and were always accompanied by small outward membrane currents. 3. Repetitive application of ACPD failed to trigger further Ca2+ release. We found that a threshold level of voltage-gated Ca2+ entry during trains of action potentials was needed to prime further mGlu-stimulated Ca2+ release. In contrast, the passage of time alone did not cause the mGlu-release system to reactivate--restoration of ACPD-stimulated Ca2+ release. The spike-mediated Ca2+ signal was unaffected by mGlu-stimulated depletion of intracellular stores. 4. These experiments demonstrate that specific mGlu receptor activation can mobilize Ca2+ in dendrites of CA1 neurons and trigger waves of Ca(2+)-induced Ca(2+)-release throughout the cell. A use-dependent relationship between voltage-gated Ca2+ entry during trains of action potentials and mGlu-stimulated Ca2+ release is suggested.
Current source density (CSD) analysis of retinal field potentials. I. Methodological considerations and depth profiles
Authors: Xu X. , Karwoski C. J.
Published: December 2017

1. The technique of current source density (CSD) analysis was used to obtain depth profiles of light-evoked source/sink distributions in the retina of the frog. 2. The effects of a number of methodological considerations on the CSD profiles were explored. Adoption of best technique leads to minimal variability and noise in the CSD profiles. Several situations that give rise to artifactual source/sinks were identified. 3. At the time of the b-wave peak, there is a large sink near the outer plexiform layer (OPL), a source at the inner limiting membrane (ILM), and a complex response at the inner plexiform layer (IPL). 4. The IPL response at light onset consists of 1) an initial, sharp sink, followed by 2) a slower source with a time course similar to the b-wave, and last 3) an even slower sink with a time course similar to the M-wave. 5. The first component of the IPL response is the current sink for the proximal negative response (PNR) elicited by a diffuse light stimulus. The PNR has current sources both proximal and distal to this layer. 6. The OPL sink underlies the b-wave. The second component of the IPL response is a source for the b-wave. Part of the ILM source also might be a b-wave source. 7. A large part of the ILM source is the current source for the M-wave. The third component of the IPL response is the M-wave sink, but it is small because it subtractively interacts with the IPL b-wave source.
Covert attention suppresses neuronal responses in area 7a of the posterior parietal cortex
Authors: Steinmetz M. A. , Connor C. E. , Constantinidis C. , McLaughlin J. R.
Published: December 2017

1. The effect of covert attention was studied in area 7a of the posterior parietal cortex of rhesus monkeys performing a spatial match-to-sample task. The task required the animals to fixate a central target light, to detect and remember the location of a transient spatial cue, and to respond when one of a series of stimuli appeared at the cued location. Neuronal responses evoked by the visual stimuli were recorded during each behavioral trial. 2. Thirty-eight percent of the neurons isolated and studied in these experiments responded to visual stimuli. The responses of 55% of the neurons tested were suppressed, and 5% enhanced for stimuli presented at the attended location. Responses in the remaining neurons (40%) were unaffected by shifts in attention. 3. Activity in 57% of the suppressed neurons was reduced to rates not significantly different from spontaneous activity. 4. The extent of suppression for individual neurons was often restricted to the attended portion of the receptive field. 5. These data suggest a potential role for these neurons in the redirection of visual attention.
Importance of unpredictability for reward responses in primate dopamine neurons
Authors: Mirenowicz J. , Schultz W.
Published: December 2017

1. We used single neuron recording techniques in two behaving monkeys to investigate the conditions in which dopamine neurons respond to primary rewarding or potentially rewarding stimuli. Animals received drops of liquid either outside behavioral tasks or as rewards during learning or established performance of an auditory reaction time task. 2. Three quarters of dopamine neurons showed a short-latency, phasic response to liquid that was delivered outside the task without being predicted by phasic stimuli. The same neurons responded to liquid reward during learning but not when task performance was established, at which time the neuronal response occurred to the conditioned, reward-predicting, movement-triggering stimulus. 3. These data suggest that the responses of dopamine neurons to rewarding or potentially rewarding liquid are due to the temporally unpredicted stimulus occurrence. A known, reward-predicting, tonic context does not prevent dopamine neurons from responding to the rewarding liquid. The responses during learning apparently occur because reward is not yet reliably predicted by a conditioned phasic stimulus. Because the unpredicted occurrence of reward is of central importance for learning, these responses allow dopamine neurons to play an important role in reward-driven learning.
Altered desensitization produces enhancement of EPSPs in neocortical neurons
Authors: Pelletier M. R. , Hablitz J. J.
Published: December 2017

1. Neocortical brain slices were prepared from rats (35–50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.
Electrophysiological and morphological characteristics of layer VI pyramidal cells in the cat motor cortex
Authors: Kang Y. , Kayano F.
Published: December 2017

1. Intracellular recordings were made from layer VI pyramidal cells in in vitro slice preparations of the cat motor cortex (area 4 gamma). Layer VI pyramidal cells were identified morphologically by intracellular injection of biocytin. 2. Of 22 layer VI pyramidal cells examined, single action potentials were followed by depolarizing afterpotentials (DAP) in 9 cells, but were not followed by DAP in the remaining 13 cells. The amplitude of DAP was 3.4 +/- 1.4 mV (mean +/- SD, n = 9) when measured from the negative peak of fast afterhyperpolarization to the peak of DAP. 3. In response to depolarizing current pulses with a duration of 300–400 ms, pyramidal cells showing DAP displayed a train of action potentials in a phasic-tonic pattern without any appreciable adaptation in the tonic firing, whereas pyramidal cells lacking DAP exhibited a weak adaptation after phasic firing. Anomalous rectification was seen in both pyramidal cells showing DAP and those lacking DAP. 4. Repetitive doublet or triplet spiking was induced in DAP-showing pyramidal cells in response to a depolarizing current pulse after injecting strong depolarizing current pulses of 400 ms duration at 1 Hz for 30–60 s, but was never induced in DAP-lacking pyramidal cells. Doublet/triplet spiking lasted 5–10 min and returned to the original single spiking. An application of CsCl induced a burst firing in DAP-showing pyramidal cells. 5. In the nine pyramidal cells showing DAP, seven cells had shorter apical dendrites that arborized extensively at layer V and terminated in the middle part of layer III. In the 13 pyramidal cells lacking DAP, 11 cells had longer apical dendrites that arborized less frequently and extended into layer II or I. Main axons could be traced into the deep white matter in 17 of the 22 layer VI pyramidal cells examined. 6. Ascending recurrent axon collaterals were more prominent in pyramidal cells with longer apical dendrites than in pyramidal cells with shorter apical dendrites. The terminal bouton-like swelling observed along the recurrent axon collaterals arising from the pyramidal cells with longer apical dendrite were distributed most densely at the level between the bottom part of layer III and the top part of layer V. In contrast, those arising from the pyramidal cells with shorter apical dendrite were distributed mainly at the levels of layers V and VI.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of associative memory function in a biophysical simulation of rat piriform cortex
Authors: Barkai E. , Bergman R. E. , Horwitz G. , Hasselmo M. E.
Published: December 2017

1. Associative memory function was analyzed in a realistic biophysical simulation of rat piriform (olfactory) cortex containing 240 pyramidal cells and 58 each of two types of inhibitory interneurons. Pyramidal cell simulations incorporated six different intrinsic currents and three different synaptic currents. We investigated the hypothesis that acetylcholine sets the appropriate dynamics for learning within the network, whereas removal of cholinergic modulation sets the appropriate dynamics for recall. The associative memory function of the network was tested during recall after simulation of the cholinergic suppression of intrinsic fiber synaptic transmission and the cholinergic suppression of neuronal adaptation during learning. 2. Hebbian modification of excitatory synaptic connections between pyramidal cells during learning of patterns of afferent activity allowed the model to show the basic associative memory property of completion during recall in response to degraded versions of those patterns, as evaluated by a performance measure based on normalized dot products. 3. During learning of multiple overlapping patterns of afferent activity, recall of previously learned patterns interfered with the learning of new patterns. As more patterns were stored this interference could lead to the exponential growth of a large number of excitatory synaptic connections within the network. This runaway synaptic modification during learning led to excessive excitatory activity during recall, preventing the accurate recall of individual patterns. 4. Runaway synaptic modification of excitatory intrinsic connections could be prevented by selective suppression of synaptic transmission at these synapses during learning. This allowed effective recall of single learned afferent patterns in response to degraded versions of those patterns, without interference from other learned patterns. 5. During learning, cholinergic suppression of neuronal adaptation enhanced the activity of cortical pyramidal cells in response to afferent input, compensating for decreased activity due to suppression of intrinsic fiber synaptic transmission. This modulation of adaptation led to more rapid learning of afferent input patterns, as demonstrated by higher values of the performance measure. 6. During recall, when suppression of excitatory intrinsic synaptic transmission was removed, continued cholinergic suppression of neuronal adaptation led to the spread of excessive activity. More stable activity patterns during recall could be obtained when the cholinergic suppression of neuronal adaptation was removed at the same time as the cholinergic suppression of synaptic transmission. 7. A realistic biophysical simulation of the effects of acetylcholine on synaptic transmission and neuronal adaptation in the piriform cortex shows that these effects act together to set the appropriate dynamics for learning, whereas removal of both effects sets the appropriate dynamics for recall.
Properties and ionic mechanisms of a metabotropic glutamate receptor-mediated slow afterdepolarization in neocortical neurons
Authors: Greene C. C. , Schwindt P. C. , Crill W. E.
Published: December 2017

1. Pyramidal neurons from layer V of rat neocortex were recorded intracellularly in a brain slice preparation to study their response to stimulation of metabotropic glutamate receptors (mGluRs) by bath application of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the nonselective agonists glutamate and quisqualate. 2. The principal postsynaptic effect of mGluR stimulation in the presence of ionotropic glutaminergic and muscarinic cholinergic antagonists was the appearance of a slow afterdepolarization (ADP) after evoked spikes. Only an afterhyperpolarization (AHP) was present in control perfusate. After 20 spikes evoked individually at 100 Hz the ADP peaked at 317 +/- 117 (SD) ms after the spike train, ranged from 1 to 12 mV in peak amplitude, and decayed over 7.4 +/- 4.7 s. This effect was not blocked by L-2-amino-3-phosphono-propionic acid (1 mM). Spikes evoked in the presence of the ionotropic glutamate receptor agonist R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) did not have an ADP. 3. A detectable ADP appeared at concentrations of 0.1 microM quisqualate or 0.5 microM 1S,3R-ACPD. Maximum ADP amplitude was obtained with 5 microM quisqualate or 100 microM 1S,3R-ACPD. The ADP appeared after a single evoked spike in most cells tested and ADP amplitude increased to a maximum as the number of spikes evoked at 100 Hz was increased to between 5 and 20. 4. The ionic mechanisms underlying the ADP were examined by ion substitution and the application of channel-blocking agents. No difference in ADP amplitude was observed when the recording electrode contained CH3SO4. instead of Cl.. The ADP was present after 3 mM extracellular Cs+ were added to block the hyperpolarization-activated cation current or when 100 microM Ba2+ were included to block voltage-gated K+ currents. The ADP was abolished when Mn2+ was substituted for Ca2+ in the perfusate or when the Ca2+ chelator 5,5'-dimethyl-bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid was included in the recording electrode. A large ADP followed Ca2+ spikes evoked in the presence of 1 microM tetrodotoxin with 20 mM tetraethylammonium in the perfusate or with Cs+ substituted for K+ in the recording electrode. The amplitude of the ADP after the Ca2+ spikes was reduced by 49% when extracellular Na+ concentration was reduced from 136 to 26 mM. 5. The voltage dependence of the ADP was examined in relation to K+ equilibrium potential (EK).(ABSTRACT TRUNCATED AT 400 WORDS)
Time course of locomotor recovery and functional regeneration in spinal cord-transected lamprey: in vitro preparations
Authors: McClellan A. D.
Published: December 2017

1. Previous studies indicate that after transection of the rostral spinal cord, larval lamprey begin to recover locomotor behavior 2 wk posttransection and recovery is complete at approximately 8 wk. To examine the mechanisms underlying behavioral recovery after spinal cord transection, in the present study the time course and extent of recovery of locomotor function was examined in in vitro brain/spinal cord preparations. With these preparations the contributions of functional regeneration of descending brain stem projections to recovery of spinal locomotor function can be examined in the absence of mechanosensory inputs and descending propriospinal relay systems. 2. In in vitro preparations from normal lamprey, stimulation in brain stem locomotor regions resulted in direct descending activation of locomotor networks in the rostral, middle, and caudal spinal cord. 3. At 4 wk posttransection, in vitro locomotor activity was usually confined to the rostral spinal cord a few millimeters below the transection site. At 8 wk posttransection locomotor activity was present in both the rostral and middle spinal cord, and spinal locomotor networks at these levels could be directly activated by restored descending projections from the brain stem. 4. At 16–32 wk posttransection locomotor activity similar to that seen in normal animals was present along the spinal cord. Additional manipulations suggest that at 32 wk posttransection descending axons from brain stem command/initiation neurons had grown for relatively long distances and could directly activate the locomotor networks in the caudal spinal cord. At each recovery time examined the ranges of locomotor parameters (cycle time, burst proportion, and intersegmental phase lag) overlapped with those in normal animals. 5. In vitro locomotor activity in spinal cord-transected animals could be recorded at progressively more caudal levels below the transection site during the course of recovery. However, locomotor activity in in vitro preparations occurred for shorter distances below the lesion than in whole animals at comparable recovery times. 6. Our recent double-labeling experiments suggest that behavioral recovery in spinal cord-transected lamprey is largely due to true regeneration of preexisting descending axons rather than development of new descending projections. Thus, these results in conjunction with our behavioral, in vitro, and anatomic data suggest that functional regeneration of descending axons from the brain, as well as other mechanisms such as descending propriospinal relay systems and mechanosensory inputs, account for the gradual restoration of locomotor function in spinal cord-transected lamprey.
Changes in synaptic integration during the growth of the lateral giant neuron of crayfish
Authors: Edwards D. H. , Yeh S. R. , Barnett L. D. , Nagappan P. R.
Published: December 2017

1. The effect of growth on the electrotonic structure and synaptic integrative properties of the lateral giant (LG) interneuron was assessed from anatomic and electrophysiological measurements of LGs in small (1–2.4 cm) and large (9–11.2 cm) crayfish and from calculated responses of mathematical models of these neurons. Postsynaptic responses of small and large LGs were compared with model responses to determine whether the differences in the neurons' responses result from growth-related changes in their physical characteristics. 2. LG neurons in the terminal abdominal ganglia of small and large crayfish are similar in shape but differ in size according to an approximately isometric pattern of growth. The soma diameter of the large LG is 2.2 times larger than the small LG, the major ipsilateral dendrite is 2.8 times longer and 3.6 times greater in diameter, and the axon is 7.6 times longer and 4.5 times greater in diameter. The projected area of the major ipsilateral dendrite of LG in the horizontal plane of the terminal abdominal ganglion is 27 times larger in the large than in the small crayfish. 3. LG's input resistance was nearly 80% smaller in the large (167 K omega) than in the small (742 K omega) crayfish when measured at or near the initial axon segment. The cell's membrane time constant displayed an opposite relationship, with the value in the large crayfish (20.9 ms) nearly two-and-a-half times larger than the value in the small crayfish (8.6 ms). 4. Simultaneous recordings were made from the distal portion of the ipsilateral dendrite and the initial axon segment of small and large LGs to determine how excitatory postsynaptic potentials (EPSPs) are attenuated or filtered by the electrotonic properties of the different sized cells. In the small LG, the fast alpha and the slower beta components of compound EPSPs evoked by sensory nerve stimulation were similarly attenuated. In the large LG, the alpha component of the compound EPSP was much more attenuated and smoothed than the slower beta component. 5. Multicompartment models of small and large LGs were constructed and used to test whether differences in the two neurons' physical properties could account for the differences in their passive response properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Azimuthal receptive fields are shaped by GABAergic inhibition in the inferior colliculus of the mustache bat
Authors: Park T. J. , Pollak G. D.
Published: December 2017

1. In this study we examine the effects of GABAergic inhibition on the response properties and the constructed azimuthal receptive fields of 54 excitatory/inhibitory (EI) neurons tuned to 60 kHz in the inferior colliculus of the mustache bat. The constructed azimuthal receptive fields predict the spike counts that would be evoked by different intensities of 60-kHz sounds presented from each of 13 azimuthal locations in the frontal sound field. 2. Action potentials were recorded with a micropipette attached to a multibarrel glass electrode. Bicuculline, an antagonist specific for gamma-aminobutyric acid-A (GABAA) receptors, was iontophoretically applied through the multibarrel electrode. Both monaural and binaural response properties were initially recorded at a variety of interaural intensity disparities (IIDs) and absolute intensities, and the same response properties were subsequently assessed while GABAergic inhibition was blocked by bicuculline. Azimuthal receptive fields both before and during the application of bicuculline were constructed from response properties obtained with earphones after correcting for the directional properties of the ear and the IIDs generated by 60-kHz sounds presented from a variety of azimuthal locations. 3. Bicuculline had virtually no effect on either the monaural or binaural properties of 19 cells (35%). The constructed azimuthal receptive fields of these cells were also unaffected by bicuculline. Presumably the properties of these cells were formed in a lower nucleus, most likely the contralateral lateral superior olive (LSO), and were imposed on the collicular cell via the crossed projection from the LSO to the inferior colliculus, which is known to be excitatory. 4. In more than half of the neurons (65%) GABAergic inhibition influenced one or more features of the cell's response properties and thus its azimuthal receptive field. Some response properties were formed in the colliculus through GABAergic inhibition, whereas others appear to have been shaped initially in a lower nucleus and then further modified by GABAergic inhibition in the inferior colliculus. Moreover, a number of features of GABAergic inhibition that acted on inferior collicular cells were evoked by stimulation of the contralateral (excitatory) ear, whereas other features were influenced by stimulation of the ipsilateral (inhibitory) ear. 5. In 20 cells (37%) blocking GABAergic inhibition reduced or abolished the inhibition evoked by the ipsilateral ear. The receptive fields of cells in which the ipsilaterally evoked inhibition was reduced by bicuculline expanded further into the ipsilateral sound field than they did before bicuculline.(ABSTRACT TRUNCATED AT 400 WORDS)