Impact of Heterogeneous Perisomatic IPSC Populations on Pyramidal Cell Firing Rates

2004 ◽  
Vol 91 (6) ◽  
pp. 2849-2858 ◽  
Author(s):  
Ildiko Aradi ◽  
Vijayalakshmi Santhakumar ◽  
Ivan Soltesz
Keyword(s):  
Computational Modeling ◽  
Pyramidal Cell ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Decay Kinetics ◽  
Potential Oscillations ◽  
Firing Rates ◽  
Ca1 Pyramidal Cells ◽  
Cell Firing ◽  
Modeling Data

Previous computational modeling studies suggested a set of rules underlying the modulation of principal cell firing rates by heterogeneity in the synaptic parameters (peak amplitude and decay kinetics) of populations of GABAergic inputs. Here we performed dynamic clamp experiments in CA1 hippocampal pyramidal cells to test these ideas in biological neurons. In agreement with the simulation studies, the effects of increasing the event-to-event variance in a population of perisomatically injected inhibitory postsynaptic current (IPSC) peak conductances caused either an increase, decrease, or no change in the firing rates of CA1 pyramidal cells depending on the mean around which the scatter was introduced, the degree of the scatter, the depolarization that the pyramidal cell received, and the IPSC reversal potential. In contrast to CA1 pyramidal cells, both model and biological CA3 pyramidal cells responded with bursts of action potentials to sudden, step-wise alterations in input heterogeneity. In addition, injections of 40-Hz IPSC conductances together with θ-modulated depolarizing current inputs to CA1 pyramidal cells demonstrated that the principles underlying the modulation of pyramidal cell excitability by heterogeneous IPSC populations also apply during membrane potential oscillations. Taken together, these experimental results and the computational modeling data show the existence of simple rules governing the interactions of heterogeneous interneuronal inputs and principal cells.

Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

2009 ◽  
Vol 102 (4) ◽  
pp. 2538-2553 ◽  
Author(s):  
Bálint Lasztóczi ◽  
Gabriella Nyitrai ◽  
László Héja ◽  
Julianna Kardos
Keyword(s):  
Pyramidal Cell ◽  
Synaptic Input ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
High Frequency Oscillation ◽  
Recurrent Seizure ◽  
Cell Firing ◽  
Ca3 Pyramidal Cells

Here we address how dynamics of glutamatergic and GABAergic synaptic input to CA3 pyramidal cells contribute to spontaneous emergence and evolution of recurrent seizure-like events (SLEs) in juvenile (P10-13) rat hippocampal slices bathed in low-[Mg2+] artificial cerebrospinal fluid. In field potential recordings from the CA3 pyramidal layer, a short epoch of high-frequency oscillation (HFO; 400–800 Hz) was observed during the first 10 ms of SLE onset. GABAergic synaptic input currents to CA3 pyramidal cells were synchronized and coincided with HFO, whereas the glutamatergic input lagged by ∼10 ms. If the intracellular [Cl−] remained unperturbed (cell-attached recordings) or was set high with whole cell electrode solution, CA3 pyramidal cell firing peaked with HFO and GABAergic input. By contrast, with low intracellular [Cl−], spikes of CA3 pyramidal cells lagged behind HFO and GABAergic input. This temporal arrangement of HFO, synaptic input sequence, synchrony of GABAergic currents, and pyramidal cell firing emerged gradually with preictal discharges until the SLE onset. Blockade of GABAA receptor-mediated currents by picrotoxin reduced the inter-SLE interval and the number of preictal discharges and did not block recurrent SLEs. Our data suggest that dynamic changes of the functional properties of GABAergic input contribute to ictogenesis and GABAergic and glutamatergic inputs are both excitatory at the instant of SLE onset. At the SLE onset GABAergic input contributes to synchronization and recruitment of pyramidal cells. We conjecture that this network state is reached by an activity-dependent shift in GABA reversal potential during the preictal phase.

scholarly journals Why are pyramidal cell firing rates increased with aging, and what can we do about it?

2008 ◽  
Vol 9 (S1) ◽  
Author(s):  
A Yadav ◽  
Christina M Weaver ◽  
Yuan Z Gao ◽  
Jennifer I Luebke ◽  
Susan L Wearne
Keyword(s):  
Pyramidal Cell ◽  
Firing Rates ◽  
Cell Firing

scholarly journals The Susceptibility of CA1 Pyramidal Cells to Cerebral Ischemia is Maintained after Neonatal, Lesion-Induced Reorganization of the Hippocampal Circuitry

1994 ◽  
Vol 14 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Niels Tønder ◽  
Flemming F. Johansen ◽  
Jens Zimmer ◽  
Nils H. Diemer
Keyword(s):  
Cerebral Ischemia ◽  
Pyramidal Cell ◽  
Neuronal Degeneration ◽  
Pyramidal Cells ◽  
Cell Loss ◽  
Transient Cerebral Ischemia ◽  
Ca1 Pyramidal Cells ◽  
Neonatal Lesion ◽  
Neonatal Lesions ◽  
Hippocampal Circuitry

Acute lesions of hippocampal pathways have been shown previously to ameliorate CA1 pyramidal cell loss after subsequent transient cerebral ischemia. In this study, we examined the effect of chronic neonatal lesion with reorganization of hippocampal circuitry on adult postischemic neuron loss in the hippocampus. Newborn rats were subjected to unilateral knife-cut lesions at various positions along the trisynaptic entorhino-dentatohippocampal pathway. Seven months later, the rats were subjected to transient cerebral ischemia using the four-vessel occlusion technique. At the time of killing 4 days later, a Nissl stain was used to demonstrate neuronal degeneration, while connective reorganization resulting from the neonatal lesions was monitored by Timm staining. In one group of rats, neonatal lesions had caused severe depletion of entorhinal projections to the septodorsal fascia dentata and hippocampus (CA1 and CA3), without any direct damage to the dorsal hippocampus itself. Another group had extensive damage of the dorsal CA3, with removal of the Schaffer collaterals from these levels to CA1, and variable damage to the entorhinal afferents. In both groups, the extent and pattern of ischemia-induced degeneration of CA1 pyramidal cells were the same on the lesioned and nonlesioned sides of the brain, demonstrating that neonatal lesions and the subsequent connective reorganization did not have a sparing effect. Seen in relationship to previous observations in adult rats of the neuroprotective actions of acute, preischemic lesions of the trisynaptic hippocampal pathway, it is concluded that CA1 pyramidal cell loss requires the presence of intact excitatory afferents rather than an intact hippocampal circuitry.

scholarly journals Computer modeling of hippocampal CA1 pyramidal cells - a tool for in silico experiments

2015 ◽  
Vol 61 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Júlia Metz ◽  
T. Szilágyi ◽  
M. Perian ◽  
K. Orbán-Kis
Keyword(s):  
Pyramidal Cell ◽  
In Silico ◽  
Action Potentials ◽  
Firing Pattern ◽  
Cell Model ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Network Activity ◽  
Ca1 Pyramidal Cells ◽  
Neuronal Network Activity

Abstract Objective. In silico experiments use mathematical models that capture as much as possible from the properties of the biological system under investigation. Our aim was to test the publicly available CA1 pyramidal cell models using the same simulation tasks, to compare them, and provide a systematic overview of their properties in order to improve the usefulness of these models as a tool for in silico experiments. Methods. Parameters describing the morphology of the cells and the implemented biophysical mechanisms were collected from the Model DB database of Sense Lab Project. This data was analyzed in correlation with the purpose for which each particular model was developed. Multicompartmental simulations were run using the Neuron modeling platform. The properties of the action potentials generated in response to current injection, the firing pattern and the dendritic back-propagation were analyzed. Results. The studied models were optimized to explore different physiological and pathological properties of the CA1 pyramidal cells. We could identify four broad classes of models focusing on: (i) initiation of the action potential, firing pattern and spike timing, (ii) dendritic backpropagation, (iii) dendritic integration of synaptic inputs and (iv) neuronal network activity. Despite the large variation of the active conductances implemented in the models, the properties of the individual action potentials were quite similar, but even the most complex models could not reproduce all studied biological phenomena. Conclusions. At the moment the “perfect” pyramidal cell model is not yet available. Our work, hopefully, will help finding the best model for each scientific question under investigation.

Role of HCO3- ions in depolarizing GABAA receptor-mediated responses in pyramidal cells of rat hippocampus

1993 ◽  
Vol 69 (5) ◽  
pp. 1541-1555 ◽  
Author(s):  
L. M. Grover ◽  
N. A. Lambert ◽  
P. A. Schwartzkroin ◽  
T. J. Teyler
Keyword(s):  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Gamma Aminobutyric Acid ◽  
Free Medium ◽  
Postsynaptic Potentials ◽  
Ca1 Pyramidal Cells ◽  
Ionic Basis

1. Activation of GABAA receptors can produce both hyperpolarizing and depolarizing responses in CA1 pyramidal cells. The hyperpolarizing response is mediated by a Cl- conductance, but the ionic basis of the depolarizing response is not clear. We compared the GABAA receptor-mediated depolarizations induced by synaptically released gamma-aminobutyric acid [GABA; depolarizing inhibitory postsynaptic potentials (dIPSPs)] with those produced by exogenous GABA (depolarizing GABA responses). Short trains of high-frequency (200 Hz) stimuli were used to generate dIPSPs. We found that dIPSPs generated by trains of stimuli and depolarizing responses to exogenous GABA were accompanied by a conductance increase and had a similar reversal potential, indicating a similar ionic basis for both responses. 2. We wished to determine whether an HCO3- current contributed to the GABAA-mediated depolarizations. We found that dIPSPs and depolarizing GABA responses were sensitive to perfusion with HCO3(-)-free medium. Interpretation of these data was complicated by the mixed nature of the responses: dIPSPs were invariably accompanied by conventional, Cl(-)-mediated fast hyperpolarizing IPSPs (fIPSPs), and response to exogenous GABA usually consisted of biphasic hyperpolarizing and depolarizing responses. However, it was sometimes possible to elicit responses to GABA that appeared purely depolarizing (monophasic depolarizing GABA responses). 3. We analyzed monophasic depolarizing GABA responses and found no change in reversal potential when slices were perfused with HCO(3-)-free medium. We also made whole-cell recordings from CA1 pyramidal cells, attempting to reduce [HCO3-]i, and compared the reversal potential for monophasic depolarizing GABA responses with similar responses recorded with fine intracellular microelectrodes. We found no difference in reversal potential. We also examined effects of the carbonic anhydrase inhibitor acetazolamide (ACTZ) on depolarizing GABA responses. ACTZ reduced these responses but did not change their reversal potential. 4. Effects of HCO(3-)-free medium were not specific to GABAA receptor-mediated responses. GABAB receptor-mediated slow IPSPs (sIPSPs) were also reduced, as were excitatory postsynaptic potentials (EPSPs). Analyses of field potentials and spontaneous fIPSPs suggested a decrease in presynaptic excitability during perfusion with HCO(3-)-free medium. In addition, pyramidal cells showed decreased input resistance when perfused with HCO(3-)-free medium. 5. The sensitivity of GABAA receptor-mediated depolarizations to HCO(3-)-free medium can be explained by a decrease in presynaptic excitability and an increased resting conductance in postsynaptic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus

2014 ◽  
Vol 369 (1635) ◽  
pp. 20120518 ◽  
Author(s):  
Peter Somogyi ◽  
Linda Katona ◽  
Thomas Klausberger ◽  
Bálint Lasztóczi ◽  
Tim J. Viney
Keyword(s):  
Pyramidal Cell ◽  
Initial Segment ◽  
Field Potential ◽  
Inverse Correlation ◽  
Pyramidal Cells ◽  
Axon Initial Segment ◽  
Gamma Activity ◽  
Gabaergic Interneurons ◽  
Potential Oscillations ◽  
Network States

The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states.

Blocking GABAA Inhibition Reveals AMPA- and NMDA-Receptor-Mediated Polysynaptic Responses in the CA1 Region of the Rat Hippocampus

1997 ◽  
Vol 77 (4) ◽  
pp. 2071-2082 ◽  
Author(s):  
V. Crépel ◽  
R. Khazipov ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
External Concentration ◽  
Physiological Concentration ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Stimulation Of

Crépel, V., R. Khazipov, and Y. Ben-Ari. Blocking GABAA inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. J. Neurophysiol. 77: 2071–2082, 1997. We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 μM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 μM), glycine (10 μM), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-d-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 μM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50–150 μm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline (10 μM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of d-2-amino-5-phosphonovalerate (50 μM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of γ-aminobutyric acid-A inhibition reveals glutamate receptor-mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.

GABA Application to Hippocampal CA3 or CA1 Stratum Lacunosum-Moleculare Excites an Interneuron Network

2002 ◽  
Vol 87 (3) ◽  
pp. 1404-1414 ◽  
Author(s):  
Katherine L. Perkins
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Current Response ◽  
Ca1 Pyramidal Cells ◽  
Graded Response ◽  
Hippocampal Ca3 ◽  
Stratum Lacunosum Moleculare

Whole cell voltage-clamp recording and focal application of the neurotransmitter γ-aminobutyric acid (GABA) were used to investigate the ability of exogenous GABA applied to different locations within the guinea pig hippocampal slice to trigger a giant GABA-mediated postsynaptic current (GPSC) in pyramidal cells. A GPSC reflects the synchronous release of GABA from a group of interneurons. Recordings were done in the presence of 4-aminopyridine (4-AP) and blockers of ionotropic glutamatergic synaptic transmission. Spontaneous GPSCs occurred rhythmically in pyramidal cells under these conditions. Brief focal pressure application of GABA (500 μM; 30–200 ms) to CA3 stratum lacunosum-moleculare (SLM) or to the border between CA3 s. radiatum (SR) and SLM triggered an “all-or-none” GPSC in CA3 and CA1 pyramidal cells that looked like the spontaneous GPSCs. During the refractory period following a spontaneous GPSC, application of GABA could not trigger a GPSC. Both spontaneous GPSCs and GPSCs triggered by exogenous GABA were blocked by suppressing synaptic transmission with high Mg2+/low Ca2+bath solution. On the other hand, focal application of GABA to CA3 s. oriens (SO) or to proximal SR did not trigger a GPSC in the CA3 pyramidal cell; instead it produced a graded response. Focal application of GABA to regions other than CA3 was also tested. Focal application of GABA to CA1 SLM always triggered a GPSC in the CA3 pyramidal cell. Focal application of GABA within the outer two-thirds of the dentate molecular layer often elicited a GPSC in the CA3 pyramidal cell. In contrast, focal application of GABA to CA1 SO, to CA1 SR, or to the hilus elicited no current response in the CA3 pyramidal cell. These data indicate that the GPSC recorded in pyramidal cells that was triggered by focal GABA application resulted from the synchronous synaptic release of GABA from activated interneurons rather than from the binding of exogenous GABA to receptors on the pyramidal cell. Furthermore, the “all-or-none” nature of the response to SLM GABA applications of different durations indicates that the exogenous GABA was exciting (directly or indirectly) some members of a network of interneurons, which in turn recruited the rest of the network, rather than individually activating each interneuron that contributed to the GPSC. Interestingly, the effective sites of GABA application—CA3 SLM, CA1 SLM, and the outer two-thirds of the dentate molecular layer—are also the sites which receive direct innervation from the entorhinal cortex in an intact animal.

Activity-Dependent Depression of Local Excitatory Connections in the CA1 Region of Mouse Hippocampus

2007 ◽  
Vol 97 (6) ◽  
pp. 3926-3936 ◽  
Author(s):  
Ann E. Fink ◽  
Joshua Sariñana ◽  
Erin E. Gray ◽  
Thomas J. O'Dell
Keyword(s):  
Pyramidal Cell ◽  
Adenosine Receptors ◽  
Low Frequency ◽  
Pyramidal Cells ◽  
Paired Pulse ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Activity Dependent ◽  
Fiber Stimulation ◽  
Paired Pulse Depression

The existence of recurrent excitatory synapses between pyramidal cells in the hippocampal CA1 region has been known for some time yet little is known about activity-dependent forms of plasticity at these synapses. Here we demonstrate that under certain experimental conditions, Schaffer collateral/commissural fiber stimulation can elicit robust polysynaptic excitatory postsynaptic potentials due to recurrent synaptic inputs onto CA1 pyramidal cells. In contrast to CA3 pyramidal cell inputs, recurrent synapses onto CA1 pyramidal cells exhibited robust paired-pulse depression and a sustained, but rapidly reversible, depression in response to low-frequency trains of Schaffer collateral fiber stimulation. Blocking GABAB receptors abolished paired-pulse depression but had little effect on low-frequency stimulation (LFS)-induced depression. Instead, LFS-induced depression was significantly attenuated by an inhibitor of A1 type adenosine receptors. Blocking the postsynaptic effects of GABAB and A1 receptor activation on CA1 pyramidal cell excitability with an inhibitor of G-protein-activated inwardly rectifying potassium channels had no effect on either paired-pulse depression or LFS-induced depression. Thus activation of presynaptic GABAB and adenosine receptors appears to have an important role in activity-dependent depression at recurrent synapses. Together, our results indicate that CA3-CA1 and CA1-CA1 synapses exhibit strikingly different forms of short-term synaptic plasticity and suggest that activity-dependent changes in recurrent synaptic transmission can transform the CA1 region from a sparsely connected recurrent network into a predominantly feedforward circuit.

Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study

2013 ◽  
Vol 109 (11) ◽  
pp. 2739-2756 ◽  
Author(s):  
Xiumin Li ◽  
Kenji Morita ◽  
Hugh P. C. Robinson ◽  
Michael Small
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Recurrent Inhibition ◽  
Aspartate Receptor ◽  
Coupled Cells ◽  
Single Spike ◽  
Cell Firing ◽  
The Impact ◽  
Apical Dendrites

The distal apical dendrites of layer 5 pyramidal neurons receive cortico-cortical and thalamocortical top-down and feedback inputs, as well as local recurrent inputs. A prominent source of recurrent inhibition in the neocortical circuit is somatostatin-positive Martinotti cells, which preferentially target distal apical dendrites of pyramidal cells. These electrically coupled cells can fire synchronously at various frequencies, including over a relatively slow range (5∼30 Hz), thereby imposing oscillatory inhibition on the pyramidal apical tuft dendrites. We examined how such distal oscillatory inhibition influences the firing of a biophysically detailed layer 5 pyramidal neuron model, which reproduced the spatiotemporal properties of sodium, calcium, and N-methyl-d-aspartate receptor spikes found experimentally. We found that oscillatory synchronization strongly influences the impact of distal inhibition on the pyramidal cell firing. Whereas asynchronous inhibition largely cancels out the facilitatory effects of distal excitatory inputs, inhibition oscillating synchronously at around 10∼20 Hz allows distal excitation to drive axosomatic firing, as if distal inhibition were absent. Underlying this is a switch from relatively infrequent burst firing to single spike firing at every period of the inhibitory oscillation. This phenomenon depends on hyperpolarization-activated cation current-dependent membrane potential resonance in the dendrite, but also, in a novel manner, on a cooperative amplification of this resonance by N-methyl-d-aspartate-receptor-driven dendritic action potentials. Our results point to a surprising dependence of the effect of recurrent inhibition by Martinotti cells on their oscillatory synchronization, which may control not only the local circuit activity, but also how it is transmitted to and decoded by downstream circuits.

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