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C M Pennartz

Publications and source records attributed to C M Pennartz.

At least 19 recordsLinked to original sources
PubMed2001

Enhanced NMDA receptor activity in retinal inputs to the rat suprachiasmatic nucleus during the subjective night.

Circadian oscillator mechanisms in the suprachiasmatic nucleus (SCN) can be reset by photic input, which is mediated by glutamatergic afferents originating in the retina. A key question is why light can only induce phase shifts of the biological clock during a restricted period of the circadian cycle, namely the subjective night. One of several possible mechanisms holds that glutamatergic transmission at retinosuprachiasmatic synapses would be altered, in particular the contribution of glutamate receptor subtypes to the postsynaptic response. By studying the contributions of NMDA and non-NMDA glutamate receptors to the retinal input to SCN in whole-cell patch-clamp recordings in acutely prepared slices, we tested the hypothesis that NMDA receptor current evoked by optic nerve activity is potentiated during the subjective night. During the day the NMDA component of the EPSC evoked by optic nerve stimulation was found less frequently and was significantly smaller in magnitude than during the night. In contrast, the non-NMDA component did not show a significant day-night difference. When the magnitude of the NMDA component was normalized to that of the non-NMDA component, the day-night difference was maintained, suggesting a selective potentiation of NMDA receptor conductance. In addition to contributing to electrically evoked EPSCs, the NMDA receptor was found to sustain a small, tonically active inward current during the night phase. No significant tonic contribution by NMDA receptors was detected during the day. These results suggest, first, a dual mode of NMDA receptor function in the SCN and, second, a clock-controlled type of receptor plasticity, which may gate the transfer of photic input to phase-shifting mechanisms operating at the level of molecular autoregulatory feedback loops.

Animals↗
PubMed1999

Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording.

The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological mechanisms underlying the circadian rhythm in firing activity. Circadian rhythmicity could not be detected either in spontaneous firing rate or in other membrane properties when whole-cell measurements were made following an initial phase shortly after membrane rupture. However, this apparent lack of rhythmicity was not due to an unhealthy slice preparation or to seal formation, as a clear day/night difference in firing rate was found in cell-attached recordings. Furthermore, in a subsequent series of whole-cell recordings, membrane properties were assessed directly after membrane rupture, and in this series we did find a significant day/night difference in spontaneous firing rate, input resistance and frequency adaptation. As concerns the participation of different subpopulations of suprachiasmatic nucleus neurons expressing circadian rhythmicity, cluster I neurons exhibited strong rhythmicity, whereas no day/night differences were found in cluster II neurons. Vasopressin-containing cells form a subpopulation of cluster I neurons and showed a more pronounced circadian rhythmicity than the total population of cluster I neurons. In addition to their strong rhythm in spontaneous firing rate they also displayed a day/night difference in membrane potential.

Action Potentials↗
PubMed1999

A reexamination of the role of GABA in the mammalian suprachiasmatic nucleus.

Three independent electrophysiological approaches in hypothalamic slices were used to test the hypothesis that gamma-amino butyric acid (GABA)A receptor activation excites suprachiasmatic nucleus (SCN) neurons during the subjective day, consistent with a recent report. First, multiple-unit recordings during either the subjective day or night showed that GABA or muscimol inhibited firing activity of the SCN population in a dose-dependent manner. Second, cell-attached recordings during the subjective day demonstrated an inhibitory effect of bath- or microapplied GABA on action currents of single SCN neurons. Third, gramicidin perforated-patch recordings showed that bicuculline increased the spontaneous firing rate during the subjective day. Therefore, electrophysiological data obtained by three different experimental methods provide evidence that GABA is inhibitory rather than excitatory during the subjective day.

Action Potentials↗
PubMed1998

Electrophysiological and morphological heterogeneity of neurons in slices of rat suprachiasmatic nucleus.

1. Whole cell patch clamp recordings of neurons in slices of the suprachiasmatic nucleus (SCN) were made in order to assess their electrophysiological and morphological heterogeneity. This assessment was accomplished by (i) quantification of intrinsic membrane properties recorded in current clamp mode, (ii) studying frequency distributions of these properties, (iii) grouping of cells based on visual inspection of data records, and (iv) use of cluster analysis methods. 2. Marked heterogeneity was found in the resting membrane potential, input resistance, time constant, rate of frequency adaptation, size of rebound depolarization (low-threshold Ca2+ potential) and regularity of firing. The frequency distribution of these membrane properties deviated significantly from a normal distribution. Other parameters, including spike amplitude and width, amplitude and rising slope of the spike after-hyperpolarization (AHP) and amplitude of the spike train AHP, showed considerable variability as well but generally obeyed a normal distribution. 3. Visual inspection of the data led to partitioning of cells into three clusters, viz. cluster I characterized by monophasic spike AHPs and irregular firing in the frequency range from 1.5 to 5.0 Hz; cluster II with biphasic spike AHPs and regular firing in the same range; and cluster III with large rebound depolarizations and biphasic spike AHPs. In a post hoc analysis, these clusters also appeared to differ in other membrane properties. This grouping was confirmed by hierarchical tree clustering and multidimensional scaling. 4. The light microscopic properties of recorded neurons were studied by biocytin labelling. Neurons had monopolar, bipolar or multipolar branching patterns and were often varicose. Axons sometimes originated from distal dendritic segments and usually branched into multiple collaterals. Many cells with extra-SCN projections also possessed intranuclear axon collaterals. We found no morphological differences between clusters except that cluster III neurons possessed more axon collaterals than cluster I or II cells. 5. These results suggest that SCN neurons are heterogeneous in some basic as well as active membrane properties and can be partitioned into at least three clusters. Cluster I and II cells fire spontaneously in a regular and irregular mode, respectively, and sustain prolonged spike trains. In contrast, cluster III cells have low firing rates but may adopt a burst-like firing mode when receiving appropriate input. While all clusters transmit output to target cells within and outside SCN, cluster III cells in particular are suggested to affect excitability of large numbers of SCN neurons by their extensive local network of axon collaterals.

Animals↗
PubMed1998

Membrane properties and morphology of vasopressin neurons in slices of rat suprachiasmatic nucleus.

Vasopressin (VP) neurons in the suprachiasmatic nucleus (SCN) are thought to be closely linked to neural mechanisms for circadian timekeeping. To gain insight into the cellular-physiological principles that govern spike-driven VP release and to examine whether VP cells can be electrophysiologically and morphologically identified by a unique combination of features, we recorded membrane properties by whole cell patch-clamp methods and stained the cells with biocytin. In current-clamp mode, VP neurons recorded during subjective daytime expressed a clear time-dependent inward rectification but no pronounced low-threshold Ca2+ potential after hyperpolarizing current pulses. Their spontaneous firing rate varied between 0.6 and 13.4 Hz and was generally tonic and irregular. Spike afterhyperpolarizations (AHPs) were steeply rising and monophasic. Spikes were preceded by depolarizing ramps mediated by a slow component of Na+ current. Spike trains evoked by depolarizing current pulses displayed frequency adaptation and were usually followed by an AHP lasting 0.5-2.0 s. Spontaneous postsynaptic potentials were present in a majority of cells. Voltage-clamp recordings revealed a Ba2+-sensitive K+ current that exerts a tonic, hyperpolarizing influence on the membrane potential. This set of membrane properties was not significantly different from other cells in the dorsomedial region and is characteristic for cluster I cells, which were described previously and are widely encountered throughout the SCN. None of the cells could be classified as belonging to cluster II or III, which were indeed found mainly outside the dorsomedial region. Morphologically, single VP neurons were characterized by compact, mono- or bipolar dendritic branching patterns and numerous varicosities throughout the dendrites. They generally possessed few axon collaterals, most of which remained inside the boundaries of the SCN but were occasionally seen to project to SCN target areas. In conclusion, VP neurons in the SCN express several active membrane poperties, including time-dependent inward rectification, frequency adaptation in spike trains, monophasic spike AHPs, and Ba2+-sensitive K+ current. VP release is proposed to be governed by tonic and irregular patterns of spontaneous firing. The electrophysiological and cytological properties of VP neurons are representative for a majority of SCN cells and define them as a subset of previously defined cluster I cells.

Action Potentials↗
PubMed1997

Functional characterization of the H-current in SCN neurons in subjective day and night: a whole-cell patch-clamp study in acutely prepared brain slices.

Neurons of the rat suprachiasmatic nucleus (SCN) exhibit a circadian rhythm in spontaneous firing rate. In this whole-cell patch-clamp study in slices, we examined the possibility that H-current (IH) contributes to the spontaneous firing rate of SCN neurons. Most of our experiments were performed during the subjective day, because this is the time epoch during which one would expect the largest excitatory effect of IH if it were to fluctuate in a circadian rhythm. Current-clamp experiments showed that blockade of IH by Cs+ (1 mM) did not influence the spontaneous firing rate and resting membrane potential. Voltage-clamp experiments revealed that IH, when activated at the resting membrane potential, is probably too small in magnitude and too slow in activation to make a significant contribution to the spontaneous firing rate. Both results suggest that IH does not significantly contribute to the spontaneous firing of SCN neurons. In addition, we investigated whether the kinetics and voltage dependence of IH were modulated in a circadian manner. However, no substantial day-night differences in IH were found. We conclude that IH, as recorded in whole-cell mode, does not contribute significantly to spontaneous firing in most SCN neurons and that this current, is more likely to be involved in 'rescuing' SCN neurons from large and long-lasting hyperpolarizations by depolarizing the membrane.

Action Potentials↗
PubMed1997

Reinforcement learning by Hebbian synapses with adaptive thresholds.

A central problem in learning theory is how the vertebrate brain processes reinforcing stimuli in order to master complex sensorimotor tasks. This problem belongs to the domain of supervised learning, in which errors in the response of a neural network serve as the basis for modification of synaptic connectivity in the network and thereby train it on a computational task. The model presented here shows how a reinforcing feedback can modify synapses in a neuronal network according to the principles of Hebbian learning. The reinforcing feedback steers synapses towards long-term potentiation or depression by critically influencing the rise in postsynaptic calcium, in accordance with findings on synaptic plasticity in mammalian brain. An important feature of the model is the dependence of modification thresholds on the previous history of reinforcing feedback processed by the network. The learning algorithm trained networks successfully on a task in which a population vector in the motor output was required to match a sensory stimulus vector presented shortly before. In another task, networks were trained to compute coordinate transformations by combining different visual inputs. The model continued to behave well when simplified units were replaced by single-compartment neurons equipped with several conductances and operating in continuous time. This novel form of reinforcement learning incorporates essential properties of Hebbian synaptic plasticity and thereby shows that supervised learning can be accomplished by a learning rule similar to those used in physiologically plausible models of unsupervised learning. The model can be crudely correlated to the anatomy and electrophysiology of the amygdala, prefrontal and cingulate cortex and has predictive implications for further experiments on synaptic plasticity and learning processes mediated by these areas.

Adaptation, Physiological↗
PubMed1997

Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current.

Neurons constituting the pacemaker of circadian rhythms, located in the suprachiasmatic nucleus, generate spontaneous firing patterns that change across the day-night cycle. Their average spontaneous firing rate is considered an important functional marker of clock activity because it is highest during daytime and low at night. In this study we investigate the ionic mechanisms underlying spontaneous firing in acutely prepared slices and dissociated neurons of the suprachiasmatic nucleus. In current-clamp mode, spontaneous action potentials were consistently preceded by depolarizing ramps. These ramps were Na+ dependent, were sensitive to tetrodotoxin (TTX), and disappeared on hyperpolarization. Ramps and associated spikes were not abolished by blockers of the H current (1 mM cesium) or calcium currents (50 microM nickel or 200 microM cadmium). In voltage-clamped neurons in slices or dissociated neurons, TTX-sensitive and Na+-dependent inward current was observed to activate well below firing threshold (-60 to -50 mV). The low-threshold component of Na+ current inactivated slowly as compared with the fast component that mediates action potentials. However, its inactivation proceeded more rapidly than has been reported for the persistent Na+ current in cortical structures. Persistent Na+ current was generally absent or small in amplitude. The voltage dependence and kinetics of the slowly inactivating component of Na+ current are consistent with the hypothesis that it is partially deinactivated during spike afterhyperpolarizations and contributes significantly to subsequent depolarizing ramps. These observations implicate the slowly inactivating component of Na+ current in ionic mechanisms governing spontaneous firing in suprachiasmatic nucleus neurons.

Action Potentials↗
PubMed1995

The ascending neuromodulatory systems in learning by reinforcement: comparing computational conjectures with experimental findings.

A central problem in cognitive neuroscience is how animals can manage to rapidly master complex sensorimotor tasks when the only sensory feedback they use to improve their performance is a simple reinforcing stimulus. Neural network theorists have constructed algorithms for reinforcement learning that can be used to solve a variety of biological problems and do not violate basic neurophysiological principles, in contrast to the back-propagation algorithm. A key assumption in these models is the existence of a reinforcement signal, which would be diffusively broadcast throughout one or several brain areas engaged in learning. This signal is further assumed to mediate up- and downward changes in synaptic efficacy by acting as a multiplicative factor in learning rules. The biological plausibility of these algorithms has been defended by the conjecture that the neuromodulators noradrenaline, acetylcholine or dopamine may form the neurochemical substrate of reinforcement signals. In this commentary, the predictions raised by this hypothesis are compared to anatomical, electrophysiological and behavioural findings. The experimental evidence does not support, and often argues against, a general reinforcement-encoding function of these neuromodulatory systems. Nevertheless, the broader concept of evaluative signalling between brain structures implied in learning appears to be reasonable and the available algorithms may open new avenues for constructing more realistic network architectures.

Adaptation, Psychological↗
PubMed1994

Muscarinic modulation of synaptic transmission in slices of the rat ventral striatum is dependent on the frequency of afferent stimulation.

Extracellular, intracellular and tight-seal patch-clamp recordings in ventral striatal slices were used to investigate whether the effectiveness of muscarinic neuromodulation of fast synaptic transmission may be dependent on the frequency of afferent stimulation. In all neurons tested, EPSPs were reversibly attenuated by muscarine or carbachol. This action was completely antagonized by atropine or pirenzepine. Several observations indicated a presynaptic site of action. In extracellular recordings, carbachol reduced the monosynaptic population spike but not the non-synaptic compound action potential. The acetylcholinesterase inhibitors eserine and pyridostigmine also induced an atropine-sensitive reduction of the EPSP. When the rate of afferent stimulation was increased, control EPSPs or EPSCs exhibited a decline in peak amplitude until reaching a steady-state value. Muscarinic modulation of steady-state EPSPs/EPSCs was significantly stronger in the range of lower frequencies (0.25-4 Hz) than at higher frequencies (8 and 12 Hz). The GABAA and GABAB-receptor/channel antagonists picrotoxin and 2-hydroxy-saclofen, the opiate receptor antagonist naloxone and atropine failed to alter the shape of the frequency-response curve. These results show that both exogenous and endogenous muscarinic receptor agonists are capable of activating a presynaptic mechanism by which fast excitatory inputs to the ventral striatum are depressed. The depressive effect is clearly stronger at lower rates of afferent stimulation than at high rates. This frequency-dependent attenuation of excitatory synaptic inputs exemplifies a new type of activity-dependent neuromodulation in central neural circuits.

Acetylcholine↗
PubMed1993

Synaptic plasticity in an in vitro slice preparation of the rat nucleus accumbens.

Extra- and intracellular recordings in slices were used to examine what types of synaptic plasticity can be found in the core of the nucleus accumbens, and how these forms of plasticity may be modulated by dopamine. Stimulus electrodes were placed at the rostral border of the nucleus accumbens in order to excite primarily infralimbic and prelimbic afferents, as was confirmed by injections of the retrograde tracer fluoro-gold. In extracellular recordings, tetanization induced long-term potentiation (LTP) of the population spike in 20 out of 53 slices. The presynaptic compound action potential did not change following LTP induction. For the intracellularly recorded excitatory postsynaptic potentiation, three types of synaptic plasticity were noted: long-term potentiation (16 out of 54 cells), decremental potentiation (eight cells) and long-term depression (LTD; six cells). No correlation was found between the occurrence of potentiation or depression and various parameters of the tetanic depolarization (e.g. peak voltage, integral under the curve). The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (50 microM; D-AP5) reduced, but did not completely prevent, the induction of LTP. The incidence of LTD was not markedly affected by D-AP5. No difference in LTP was found when comparing slices bathed in dopamine (10 microM) and controls. Likewise, slices treated with a mixture of the D1 receptor antagonist Sch 23390 (1 microM) and the D2 antagonist S(-)-sulpiride (1 microM) generated a similar amount of LTP as controls. In conclusion, both LTP and LTD can be induced in a key structure of the limbic-innervated basal ganglia. LTP in the nucleus accumbens strongly depends on N-methyl-D-aspartate receptor activity, but is not significantly affected by dopamine.

2-Amino-5-phosphonovalerate↗
PubMed1993

Responses of the nucleus accumbens following fornix/fimbria stimulation in the rat. Identification and long-term potentiation of mono- and polysynaptic pathways.

The nucleus accumbens occupies a strategic position as an interface between limbic cortex and midbrain structures involved in motor performance. The fornix-fimbria carries limbic inputs to the ventral striatum, namely by way of fibers originating in the CA1/subiculum and projecting to the nucleus accumbens. It also carries fibers arising in the septal area that project to the hippocampal formation, and projection fibers to other areas of the rostral forebrain from Ammon's horn. Electrical stimulation of this bundle causes characteristic field potentials both in the nucleus accumbens and in the subiculum. In rats, under halothane anesthesia, the responses evoked by fornix/fimbria stimulation in the nucleus accumbens consist of two main positive peaks (at 10 and 25 ms, referred to as P10 and P25, respectively). P10 represents monosynaptic activation. We hypothesized that P25 reflects the activation of a polysynaptic loop, i.e. a fornix-fimbria hippocampal loop in series with the fibers that arise in the subiculum and project to the nucleus accumbens. To test this hypothesis, we reversibly blocked the fibers projecting caudally to the hippocampus by a local anesthetic (lidocaine) and the glutamatergic transmission through the CA1/subiculum by a local injection of kynurenic acid. Both manipulations yielded a reversible depression of about 90% of the P25 component while P10 remained unaffected as expected. In concert a strong reduction (to 24-31%) of control values of the responses evoked in the subiculum was seen. The dynamics of the mono- and polysynaptic pathways differ markedly. The synaptic responses through both pathways are enhanced by paired-pulse stimulation, but the polysynaptic pathway is facilitated in a much stronger way. Following a tetanus (50 Hz, 2 s duration) applied to the fornix/fimbria, the P10 component of the nucleus accumbens responses showed an immediate increase by a factor of about 2 followed by a phase of gradual decrement with half-decay time of about 10 min, after which a persistent long-term potentiation of about 25% above control level was maintained for the rest of the experiment (max 90 min). The P25 component showed a transient 10-fold potentiation with return to control values after about 10 min. In contrast to the P25 elicited by a conditioning stimulus, the P25 component elicited by a second stimulus delivered at an interval of 100 ms (test stimulus) showed a persistent long-term potentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Differential membrane properties and dopamine effects in the shell and core of the rat nucleus accumbens studied in vitro.

Electrophysiological differences between the shell and core of the rat nucleus accumbens were investigated by intracellular recordings from an in vitro slice preparation. The average input resistance of neurons recorded in the shell was larger than in the core. Neurons in the core were characterized by a more negative resting membrane potential than neurons in the shell. Furthermore, bath-applied dopamine attenuated synaptic responses recorded in the shell, but not in the core. Thus, the two main subregions of the nucleus accumbens differ both in basal membrane properties and in dopaminergic modulation of synaptic transmission.

Action Potentials↗
PubMed1992

Presynaptic dopamine D1 receptors attenuate excitatory and inhibitory limbic inputs to the shell region of the rat nucleus accumbens studied in vitro.

1. Intracellular recordings were made from the shell region of the nucleus accumbens in an in vitro slice preparation. The mean resting membrane potential, input resistance, and action potential amplitude of these neurons were -76 +/- 1 mV, 87 +/- 5 M omega and 94 +/- 2 mV (N = 108), respectively. A sample of these neurons (N = 18) was identified as medium spiny neurons with the use of the biocytin-avidin labeling technique. 2. Electrical stimulation of the fornix, subcortical fibers, or neuropil within the nucleus accumbens shell itself elicited a depolarizing postsynaptic potential (PSP). Dopamine (10-100 microM) attenuated PSPs elicited by stimulation of all of these sites. In a paired-pulse stimulation protocol, dopamine was observed to enhance the facilitation of the test response with respect to the conditioning response. 3. The suppressive effect of dopamine was mimicked by the D1 receptor agonist SKF 82958 (10-30 microM), whereas the D2 receptor agonist quinpirole (10-30 microM) was ineffective. The action of dopamine was antagonized by the D1 receptor antagonist Sch 23390 (10-30 microM), but not by the D2 receptor antagonist sulpiride (10-50 microM) or various adrenergic receptor antagonists. 4. The PSP was usually composed of an excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence. Dopamine equally attenuated the excitatory and inhibitory component of the synaptic response. The attenuation of both EPSP and IPSP did not depend on membrane potential. 5. Dopamine effects on the resting membrane potential and input resistance were variable and did not correlate with changes in the PSP. Two further indications were found in favor of a presynaptic locus of dopaminergic modulation. First, the time course of the PSP was not altered during dopamine application. Second, dopamine did not attenuate depolarizations induced by bath-applied L-glutamate. In extracellular recordings, it was found that dopamine reduced the population spike but not the presynaptic fiber volley. 6. These findings strongly indicate that dopaminergic modulation of synaptic responses in neurons located in the accumbens shell region is mediated by presynaptic D1 receptors. Notably, dopamine does not exert a purely inhibitory effect on synaptic excitability in the nucleus accumbens, because it suppresses both the excitatory and inhibitory component of the synaptic response.

Afferent Pathways↗