Biomedical subjects

A J Berger

Publications and source records attributed to A J Berger.

At least 19 recordsLinked to original sources

PubMed2000

Determinants of respiratory motoneuron output.

The respiratory motoneuron is the critical link between the neural elements responsible for respiratory rhythm generation and the respiratory muscles. Studies of respiratory motoneurons provide important information on the mechanisms that govern respiratory motor output because of the obligatory synapse that exists between these respiratory motoneurons and the respiratory muscle fibers they innervate. This review focuses almost exclusively upon one type of respiratory motoneuron, the hypoglossal motoneuron. Intrinsic properties (membrane properties and ion channels) as well as fast excitatory and inhibitory synaptic transmission to these motoneurons have been extensively studied during the last 10 years. This review summarizes many of these new findings. It is hoped that some of these findings can be generalized to all respiratory motoneurons and these will be of importance in formulating models that can predict the behavior of these critical elements in the respiratory system.

Animals↗

PubMed2000

Effect of ethanol upon respiratory-related hypoglossal nerve output of neonatal rat brain stem slices.

The actions of ethanol (EtOH) on the respiratory output of the neonatal rat brain stem slice preparation in vitro are described. Ethanol inhibited respiratory-related hypoglossal nerve activity in a dose-dependent manner. The effect of EtOH was evident within 5 min and was reversible on EtOH washout. The actions of EtOH were qualitatively similar to those of two other alcohols, methanol and octanol. We investigated the dose-response relationship for each alcohol and determined that the order of potency was methanol < EtOH << octanol, with EC(50) values of 291 mM, 39.7 mM, and 49.2 microM respectively. Application of either strychnine (5 microM) or bicuculline (5 microM) alone, partially but not significantly, reversed the inhibition of respiratory-related hypoglossal nerve activity produced by 50 mM EtOH. Preincubation of rhythmic slices with a combination of both strychnine and bicuculline (both 5 microM) partially, but significantly, blocked the inhibitory actions of EtOH, suggesting that other mechanisms also play a role in the action of EtOH. Preincubation of the slices with 25 microM APV reduced the relative degree of inhibition caused by EtOH suggesting that N-methyl-D-aspartate (NMDA)-receptor-mediated events can be affected by EtOH. Furthermore inhibition of protein kinase C by incubation with 100 nM staurosporine also reduced the efficacy of EtOH. These results suggest that the actions of EtOH may be mediated via glycine, GABA(A), and NMDA receptors and that activation of protein kinase C is involved in the EtOH-induced inhibition of respiratory-related hypoglossal nerve activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Contribution of single-channel properties to the time course and amplitude variance of quantal glycine currents recorded in rat motoneurons.

The amplitude of spontaneous, glycinergic miniature inhibitory postsynaptic currents (mIPSCs) recorded in hypoglossal motoneurons (HMs) in an in vitro brain stem slice preparation increased over the first 3 postnatal weeks, from 42 +/- 6 pA in neonate (P0-3) to 77 +/- 11 pA in juvenile (P11-18) HMs. Additionally, mIPSC amplitude distributions were highly variable: CV 0.68 +/- 0.05 (means +/- SE) for neonates and 0.83 +/- 0.06 for juveniles. We wished to ascertain the contribution of glycine receptor (GlyR)-channel properties to this change in quantal amplitude and to the amplitude variability and time course of mIPSCs. To determine whether a postnatal increase in GlyR-channel conductance accounted for the postnatal change in quantal amplitude, the conductance of synaptic GlyR channels was determined by nonstationary variance analysis of mIPSCs. It was 48 +/- 8 pS in neonate and 46 +/- 10 pS in juvenile HMs, suggesting that developmental changes in mIPSC amplitude do not result from a postnatal alteration of GlyR-channel conductance. Next we determined the open probability (Popen) of GlyR channels in outside-out patches excised from HMs to estimate the contribution of stochastic channel behavior to quantal amplitude variability. Brief (1 ms) pulses of glycine (1 mM) elicited patch currents that closely resembled mIPSCs. The GlyR channels' Popen, calculated by nonstationary variance analysis of these currents, was approximately 0.70 (0.66 +/- 0.09 in neonates and 0.72 +/- 0.05 in juveniles). The decay rate of patch currents elicited by brief application of saturating concentrations of glycine (10 mM) increased postnatally, mimicking previously documented changes in mIPSC time course. Paired pulses of glycine (10 mM) were used to determine if rapid GlyR-channel desensitization contributed to either patch current time course or quantal amplitude variability. Because we did not observe any fast desensitization of patch currents, we believe that fast desensitization of GlyRs underlies neither phenomenon. From our analysis of glycinergic patch currents and mIPSCs, we draw three conclusions. First, channel deactivation is the primary determinant of glycinergic mIPSC time course, and postnatal changes in channel deactivation rate account for observed developmental changes in mIPSC decay rate. Second, because GlyR-channel Popen is high, differences in receptor number between synapses rather than stochastic channel behavior are likely to underlie the majority of quantal variability seen at glycinergic synapses throughout postnatal development. We estimate the number of GlyRs available at a synapse to be on average 27 in neonate neurons and 39 in juvenile neurons. Third, this change in the calculated number of GlyRs at each synapse may account for the postnatal increase in mIPSC amplitude.

Age Factors↗

PubMed1999

Cotransmission of GABA and glycine to brain stem motoneurons.

Using whole cell patch-clamp recording in a rat brain stem slice preparation, we found that gamma-aminobutyric acid (GABA) and glycine act as cotransmitters to hypoglossal motoneurons (HMs). Focal application of GABA and glycine onto a single HM revealed that GABAA and glycine receptors are present on the same neuron. To demonstrate that HMs receive both GABAergic and glycinergic synaptic inputs, we simultaneously recorded GABAA- and glycine-receptor-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in single HMs. GABAergic and glycinergic mIPSCs were differentiated based on their kinetics and modulation by pentobarbital. Specifically, GABAA-receptor-mediated events decayed more slowly than glycine-receptor-mediated events. GABAergic response decay kinetics were prolonged by pentobarbital, whereas glycinergic response decay kinetics remained unchanged. The distinct kinetics of the glycine- and GABAA-receptor-mediated synaptic events allowed us to record dual component mIPSCs, mIPSCs that are mediated by both receptor types. These data suggest that GABA and glycine are colocalized in the same presynaptic vesicle and are coreleased from presynaptic terminals opposed to motoneurons.

Animals↗

PubMed1998

G alphas-induced neurodegeneration in Caenorhabditis elegans.

We describe a genetic model for neurodegeneration in the nematode Caenorhabditis elegans. Constitutive activation of the GTP-binding protein Galphas induces neurodegeneration. Neuron loss occurs in two phases whereby affected cells undergo a swelling response in young larvae and subsequently die sometime during larval development. Different neural cell types vary greatly in their susceptibility to Galphas-induced cytotoxicity, ranging from 0 to 88% of cells affected. Mutations that prevent programmed cell death do not prevent Galphas-induced killing, suggesting that these deaths do not occur by apoptosis. Mutations in three genes protect against Galphas-induced cell deaths. The acy-1 gene is absolutely required for neurodegeneration, and the predicted ACY-1 protein is highly similar (40% identical) to mammalian adenylyl cyclases. Thus, Gs-induced neurodegeneration is mediated by the second messenger cAMP. Mutations in the unc-36 and eat-4 genes are partially neuroprotective, which indicates that endogenous signaling modulates the severity of the neurotoxic effects of Galphas. These experiments define an intracellular signaling cascade that triggers a necrotic form of neurodegeneration.

Adenylyl Cyclases↗

PubMed1998

An enhanced algorithm for linear multivariate calibration.

We present a new method of linear multivariate calibration that can generate better prediction results than those obtained by partial least squares (PLS). This is accomplished by incorporating the spectrum of the desired species into the calibration procedure. The method combines the advantages of different standard methods and is therefore called hybrid linear analysis (HLA). In side-by-side tests using both simulated and experimental data, HLA produced lower prediction errors than PLS in all instances. We recommend HLA over PLS in situations where the spectrum of the desired species is available.

Algorithms↗

PubMed1998

Development of glycinergic synaptic transmission to rat brain stem motoneurons.

Using an in vitro rat brain stem slice preparation, we examined the postnatal changes in glycinergic inhibitory postsynaptic currents (IPSCs) and passive membrane properties that underlie a developmental change in inhibitory postsynaptic potentials (IPSPs) recorded in hypoglossal motoneurons (HMs). Motoneurons were placed in three age groups: neonate (P0-3), intermediate (P5-8), and juvenile (P10-18). During the first two postnatal weeks, the decay time course of both unitary evoked IPSCs [mean decay time constant, taudecay = 17.0 +/- 1.6 (SE) ms in neonates and 5.5 +/- 0.4 ms in juveniles] and spontaneous miniature IPSCs (taudecay = 14.2 +/- 2.4 ms in neonates and 6.3 +/- 0.7 ms in juveniles) became faster. As glycine uptake does not influence IPSC time course at any postnatal age, this change most likely results from a developmental alteration in glycine receptor (GlyR) subunit composition. We found that expression of fetal (alpha2) GlyR subunit mRNA decreased, whereas expression of adult (alpha1) GlyR subunit mRNA increased postnatally. Single GlyR-channels recorded in outside-out patches excised from neonate motoneurons had longer mean burst durations than those from juveniles (18.3 vs. 11.1 ms). Concurrently, HM input resistance (RN) and membrane time constant (taum) decreased (RN from 153 +/- 12 MOmega to 63 +/- 7 MOmega and taum from 21.5 +/- 2.7 ms to 9.1 +/- 1.0 ms, neonates and juveniles, respectively), and the time course of unitary evoked IPSPs also became faster (taudecay = 22.4 +/- 1.8 and 7.7 +/- 0.9 ms, neonates vs. juveniles, respectively). Simulated synaptic currents were used to probe more closely the interaction between IPSC time course and taum, and these simulations demonstrated that IPSP duration was reduced as a consequence of postnatal changes in both the kinetics of the underlying GlyR channel and the membrane properties that transform the IPSC into a postsynaptic potential. Additionally, gramicidin perforated-patch recordings of glycine-evoked currents reveal a postnatal change in reversal potential, which is shifted from -37 to -73 mV during this same period. Glycinergic PSPs are therefore depolarizing and prolonged in neonate HMs and become faster and hyperpolarizing during the first two postnatal weeks.

Animals↗

PubMed1998

Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses.

Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336-3340, 1998. At central synapses occupation of glycine binding sites of N-methyl--aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R-mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by -serine. The effects of glycine were observed only at concentrations (100 microM or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, -serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is likely to be stabilized by a powerful glycine transport mechanism.

Animals↗

PubMed1997

Clonidine reduces hyperpolarization-activated inward current (Ih) in rat hypoglossal motoneurons.

We used intracellular recording techniques to investigate the actions of clonidine on hypoglossal motoneurons (HMs) in rat brainstem slices. Clonidine (10-100 microM) produced a small (2-6 mV), dose-dependent hyperpolarization in HMs, accompanied by an increase in peak input resistance (RN). It also slowed the time course of the depolarizing 'sag' of the voltage response to constant hyperpolarizing current steps. These effects were mimicked by the alpha2-adrenoceptor (alpha2-AR) agonist guanabenz, but not by the Ih-imidazoline receptor agonists moxonidine or rilmenidine. Recorded in single-electrode voltage clamp mode, clonidine decreased input conductance of HMs and reduced the amplitude of a hyperpolarization-activated inward current (Ih). Clonidine's effect on Ih was three-fold: it shifted the half-activation voltage (V1/2) in the hyperpolarizing direction (by 4.4 +/- 0.7 mV at a dose of 10 microM), decreased the maximal current (by approximately 20%), and slowed the time course of Ih activation at all voltage steps. At the most hyperpolarized potential steps, clonidine slowed activation of Ih dramatically, yielding a striking increase in the activation time constant. The alpha2-AR antagonists yohimbine and idazoxan reduced clonidine's effect on V1/2 and on the Ih activation time course, but neither blocked clonidine's reduction of the maximal current, nor its strong slowing of Ih activation at the most hyperpolarized steps. We were unable to mimic or occlude clonidine's actions with the adenylate cyclase inhibitor SQ 22536 nor with the non-specific protein kinase inhibitor H-7. We conclude that clonidine hyperpolarizes HMs via a reduction of the amount of Ih that is active at rest, and that the response is mediated in part by alpha2-ARs. Some effects of clonidine on these neurons do not appear to be receptor-mediated, and may be due to physical block by clonidine of Ih channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1997

NMDA and non-NMDA receptors are co-localized at excitatory synapses of rat hypoglossal motoneurons.

We used whole-cell patch clamp recordings in a rat brainstem slice preparation to characterize the properties of miniature excitatory postsynaptic currents (mEPSCs) in hypoglossal motoneurons. The distinct kinetic characteristics of N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated synaptic responses allowed us to study dual component mEPSCs mediated by the two receptor types. Using this approach, NMDA and non-NMDA receptors were found to be co-localized at the same synaptic locations. In addition, some sites contain only NMDA receptors since a large proportion of mEPSCs were apparently mediated by NMDA receptors only. Furthermore, the amplitudes of pharmacologically isolated NMDA receptor-mediated mEPSCs were highly variable in individual cells and their decay kinetics were modulated by membrane potential.

Animals↗

PubMed1997

Osmolarity modulates K+ channel function on rat hippocampal interneurons but not CA1 pyramidal neurons.

1. Whole-cell and single-channel recording methods were used in conjunction with infrared video microscopy techniques to examine the properties of voltage-activated potassium channels in hippocampal neurons during the application of hyposmolar solutions to hippocampal slices from rats. 2. Hyposmolar external solutions (osmolarity reduced by 10% to 267 mosmol l-1) produced a significant potentiation of voltage-activated K+ current on lacunosum/moleculare (L/M) hippocampal interneurons, but not on CA1 and subiculum pyramidal neurons. Hyperpolarization-activated (IH) and leak currents were not altered during the application of hyposmolar solutions in all cell types. 3. Mean channel open time and the probability of channel opening were dramatically increased under hyposmolar recording conditions for outside-out patches from L/M interneurons; no changes were observed for patches from CA1 pyramidal neurons. Mean current amplitude and the threshold for channel activation were not affected by hyposmotic challenge. 4. Hyposmolar external solutions produced a significant reduction in the firing frequency of L/M interneurons recorded in current-clamp mode. Hyposmolar solutions had no effect on resting membrane potential, action potential amplitude or duration, and spike after-hyperpolarization amplitude. 5. These results indicate that selective modulation of interneuron ion channel activity may be a critical mechanism by which osmolarity can regulate excitability in the central nervous system.

Animals↗

PubMed1997

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

Animals↗

PubMed1997

Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy.

We report the determinations of glucose concentrations in human whole blood samples made using near-infrared Raman spectroscopy. Raman spectra of blood samples with above-physiological levels of glucose were acquired for 5 min through the wall of a cuvette via fiber optics. Partial least squares analysis was used to predict glucose concentrations in the samples. A root mean squared prediction error of 3.6 mM glucose was achieved with a correlation coefficient of 0.99 between reference and predicted values. This result is the first step in evaluating the potential of near-infrared Raman spectroscopy to perform blood glucose measurement with clinical accuracy. The technique is capable of measuring the concentration of other Raman-active blood constituents; as an example, bicarbonate was also measured. The method could eventually be useful for direct measurement of tissue analytes.

Blood Chemical Analysis↗

PubMed1996

Presynaptic inhibition by serotonin: a possible mechanism for switching motor output of the hypoglossal nucleus.

We examined the influence of serotonin (5-HT), an important state-dependent neuromodulator, on synaptic transmission to hypoglossal motoneurons (HMs). Our data demonstrate that 5-HT acts presynaptically to inhibit excitatory (glutamatergic) synaptic currents recorded in HMs. We discuss this result in relation to the role of 5-HT in state-dependent modulation of respiration-related activity in HMs.

Culture Techniques↗

PubMed1996

Development of hypoglossal motoneurons.

Hypoglossal motoneurons (HMs) are brain stem motoneurons that innervate tongue muscles. Their function is critical in the control of the upper airway. Results from in vitro studies of rat HMs have shown that properties of HMs change during the postnatal period. For example, these studies have uncovered changes in HM morphology and electrical properties (both in ion channels and firing properties) as well as changes in chemical synaptic transmission to HMs during the postnatal period. Morphologically, a marked reduction in complexity of the dendritic tree takes place over the first 2 wk postnatal. In terms of electrical properties, a substantial and progressive fall in motoneuronal input resistance occurs during the first month of life, due to a decrease in specific membrane resistivity. This is primarily responsible for the progressive increase in rheobase and consequent reduction in cell excitability. In addition, the densities of at least two types of membrane ion channels are altered in early postnatal life, contributing to changes in their electroresponsive properties. On the one hand, the depolarizing mixed cationic current that is activated by membrane hyperpolarization was found to be approximately 10-fold larger in adult than in neonatal HMs. By contrast, neonatal HMs possess a transient low-voltage-activated T-type Ca2+ channel with a low single-channel conductance (approximately 7 pS), the density of which rapidly declines during the early postnatal period. The functional relevance of these and other changes occurring during the postnatal period is discussed.

Age Factors↗

PubMed1996

Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons by serotonin.

1. In a brain stem slice preparation, we recorded glutamatergic excitatory postsynaptic currents (EPSCs) in hypoglossal motoneurons (HMs) evoked by extracellular stimulation in the reticular formation just ipsilateral to the hypoglossal motor nucleus (n. XII). Serotonin (5-HT) inhibited glutamatergic synaptic transmission in a dose-dependent fashion as indicated by a reduction in the evoked EPSC (eEPSC) peak amplitude to 46 +/- 2% (mean +/- SE, n = 26) of control (5-HT 10 microM). This effect was not voltage dependent, as the eEPSC reversal potential was not altered (n = 5). Additionally, 5-HT decreased the rate of rise of the eEPSC to 41 +/- 2% of control (n = 14). Blockade of N-methyl-D-aspartate-receptor-channels by D(-)-2-amino-5-phosphonopentanoic acid (50 microM) or of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor-channels by 6,7-dinitro-quinoxaline (20 microM) did not alter the relative reduction of the eEPSC amplitude by 5-HT (n = 7 and 3, respectively). 2. In the presence of tetrodotoxin (1 microM), bath application of 5-HT did not reduce postsynaptic glutamate currents elicited by pressure ejection of L-glutamate (1 mM) onto HMs (n = 5), and it increased the median interevent interval of spontaneous miniature EPSCs (mEPSCs) to 178 +/- 12% of control (n = 4), suggesting that 5-HT acts presynaptically to reduce the probability of vesicle release. mEPSC amplitude was decreased slightly in three of four cells (median amplitude = 92 +/- 3% of control). 3. The specific 5-HT1B receptor agonist [3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one] (1 microM) mimicked 5-HT in its effect on eEPSCs (eEPSC amplitude reduced to 31 +/- 5% of control; rate of rise reduced to 40 +/- 4% of control, n = 10 and 5, respectively) and mEPSCs (median interevent interval increased to 231 +/- 36% of control; median mEPSC amplitude = 102 +/- 3% of control, n = 5). Additionally, 5-HT-mediated inhibition was not blocked by coapplication of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine hydrobromide (1 microM), a 5-HT1A antagonist, and 3-[2-[4-(4-flurobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quin azolinedione tartrate (1 microM), a 5-HT2A/2C antagonist (n = 4). These data indicate that the 5-HT effect is primarily 5-HT1B receptor mediated. 4. We conclude that 5-HT, acting through presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic transmission by reducing the probability of vesicle release.

Animals↗

PubMed1996

Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors.

1. Whole cell recordings of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the reticular formation were made from visualized hypoglossal motoneurons (HMs) in rat brain stem slices. 2. Carbachol, muscarine, or physostigmine reduced EPSC amplitude to 50 +/- 3%, 37 +/- 3%, and 54 +/- 7% (mean +/- SE) of control, respectively; effects of carbachol and physostigmine were antagonized by atropine (1-2 microM). EPSC depression was most effectively antagonized by methoctramine, an M2 muscarinic acetylcholine receptor (mAChR) antagonist with a high affinity constant (pKB) of 8.07 for the receptor mediating this response, whereas pirenzepine, an M1 mAChR antagonist, had a pKB of < 7.0, showing that EPSC depression was mediated by the M2 mAChR. 3. Postsynaptic properties of HMs (holding current and input resistance), EPSCs (reversal potential, rise time, half-width, and decay time constant), and postsynaptic glutamate-gated currents (amplitude and waveform) were not altered by carbachol or muscarine. 4. Muscarine did not decrease presynaptic neuron excitability, because the frequency of spontaneous EPSCs in HMs in the absence of tetrodotoxin (TTX) was either unchanged or increased. Leak and action currents of reticular formation neurons were not significantly altered by muscarine. In contrast, with TTX present, the frequency of spontaneous miniature glutamatergic EPSCs in HMs was decreased by both carbachol (mean change = 203 +/- 46%) and muscarine (mean change = 185 +/- 26%), with no change in miniature EPSC amplitude distribution. 5. Muscarinic depression of excitatory transmission to HMs thus occurs at the presynaptic terminal, most probably affecting release mechanisms downstream from calcium entry, and is likely to be significant during rapid eye movement sleep, possibly underlying the loss of tongue tone and inspiratory activity during this state.

Animals↗

PubMed1995

Repetitive firing properties of developing rat brainstem motoneurones.

1. The repetitive firing properties of neonatal and adult rat hypoglossal motoneurones (HMs) were investigated in a brainstem slice preparation. Neonatal HMs could be classified into two main groups: (1) neurones with a decrementing or adapting firing pattern (type D); exhibiting an early and a late phase; and (2) neurones with an incrementing or accelerating firing pattern (type I). 2. The pattern of repetitive firing changed markedly during development. While most HMs recorded from young rats (< postnatal day (P) 4) were type D, the majority of HMs recorded during the second postnatal week were type I. In adults (> P21), nearly all HMs had a decrementing firing pattern, characterized by a brief period of adaptation and high steady-state firing rates. 3. The calcium-dependent after-hyperpolarization (AHP) was shortest in type I neonatal HMs, and decreased in amplitude during trains of action potentials (APs). In type D neurones, these same trains caused a slight enhancement of AHP amplitude. In adult HMs, with a decrementing firing pattern, trains of APs also caused summation of the AHP. 4. Type D neonatal HMs showed a progressive prolongation of the AP during repetitive firing. In contrast, type I neonatal HMs had almost no change in AP duration. In adult HMs the AP was short and experienced only a modest increase in duration during fast repetitive firing. 5. The function relating steady-state firing frequency to injected current (f-I curve) was linear. The mean steady-state f-I slope was significantly higher in neonates than in adults (approximately 30 vs. approximately 20 Hz nA-1), and was weakly correlated with input resistance. The f-I slope was negatively correlated with AHP duration in neonatal HMs only. In addition, for a given AHP duration the slope was higher in neonatal HMs. 6. Two threshold behaviours were observed among neonatal HMs: (a) a progressive rhythmic firing threshold, and (b) a sudden transition from subthreshold to regular repetitive firing. Current threshold for repetitive firing was strongly correlated with cell input conductance. Type I neonatal HMs had higher minimal steady firing rates (fmin) than type D HMs. In neonates, fmin was strongly correlated with AHP duration. Adult HMs showed a weaker correlation between these two parameters, and fmin was higher than predicted by AHP duration. 7. In summary, HMs responded to depolarizing current pulses with different firing patterns during postnatal development.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗