Regulation of IPSP Theta Rhythm by Muscarinic Receptors and Endocannabinoids in Hippocampus

2005 ◽  
Vol 94 (6) ◽  
pp. 4290-4299 ◽  
Author(s):  
Christian G. Reich ◽  
Miranda A. Karson ◽  
Sergei V. Karnup ◽  
Lauren M. Jones ◽  
Bradley E. Alger
Keyword(s):  
Pyramidal Cell ◽  
Acetylcholine Receptors ◽  
Theta Rhythm ◽  
Pyramidal Cells ◽  
Muscarinic Acetylcholine Receptors ◽  
Mammalian Brain ◽  
Ca1 Region ◽  
Theta Frequency ◽  
Hippocampal Theta ◽  
Apical Dendrites

Theta rhythms are behaviorally relevant electrical oscillations in the mammalian brain, particularly the hippocampus. In many cases, theta oscillations are shaped by inhibitory postsynaptic potentials (IPSPs) that are driven by glutamatergic and/or cholinergic inputs. Here we show that hippocampal theta rhythm IPSPs induced in the CA1 region by muscarinic acetylcholine receptors independent of all glutamate receptors can be briefly interrupted by action potential–induced, retrograde endocannabinoid release. Theta IPSPs can be recorded in CA1 pyramidal cell somata surgically isolated from CA3, subiculum, and even from their own apical dendrites. These results suggest that perisomatic-targeting interneurons whose output is subject to inhibition by endocannabinoids are the likely source of theta IPSPs. Interneurons having these properties include the cholecystokinin-containing cells. Simultaneous recordings from pyramidal cell pairs reveal synchronous theta-frequency IPSPs in neighboring pyramidal cells, suggesting that these IPSPs may help entrain or modulate small groups of pyramidal cells.

scholarly journals Linking minimal and detailed models of CA1 microcircuits reveals how theta rhythms emerge and how their frequencies are controlled

2020 ◽  
Author(s):  
Alexandra P Chatzikalymniou ◽  
Melisa Gumus ◽  
Anton R Lunyov ◽  
Scott Rich ◽  
Jeremie Lefebvre ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Theta Rhythm ◽  
Computational Models ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Minimal Models ◽  
Detailed Model ◽  
Theta Frequency ◽  
Hippocampal Theta

AbstractThe wide variety of cell types and their inherent biophysical complexities pose a challenge to our understanding of oscillatory activities produced by cellular-based computational models. This challenge stems from the high-dimensional and multi-parametric nature of these systems. To overcome this issue, we implement systematic comparisons of minimal and detailed models of CA1 microcircuits that generate intra-hippocampal theta rhythms (3-12 Hz). We leverage insights from minimal models to guide detailed model explorations and obtain a cellular perspective of theta generation. Our findings distinguish the pyramidal cells as the theta rhythm initiators and reveal that their activity is regularized by the inhibitory cell populations, supporting an ‘inhibition-based tuning’ mechanism. We find a strong correlation between the pyramidal cell input current and the resulting LFP theta frequency, establishing that the intrinsic pyramidal cell properties underpin network frequency characteristics. This work provides a cellular-based foundation from which in vivo theta activities can be explored.

scholarly journals Presynaptic cholinergic neuromodulation alters the temporal dynamics of short-term depression at parvalbumin-positive basket cell synapses from juvenile CA1 mouse hippocampus

2015 ◽  
Vol 113 (7) ◽  
pp. 2408-2419 ◽  
Author(s):  
J. Josh Lawrence ◽  
Heikki Haario ◽  
Emily F. Stone
Keyword(s):  
Pyramidal Cell ◽  
Acetylcholine Receptors ◽  
Temporal Dynamics ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Transient ◽  
Muscarinic Acetylcholine Receptors ◽  
Presynaptic Calcium

Parvalbumin-positive basket cells (PV BCs) of the CA1 hippocampus are active participants in theta (5–12 Hz) and gamma (20–80 Hz) oscillations in vivo. When PV BCs are driven at these frequencies in vitro, inhibitory postsynaptic currents (IPSCs) in synaptically connected CA1 pyramidal cells exhibit paired-pulse depression (PPD) and multiple-pulse depression (MPD). Moreover, PV BCs express presynaptic muscarinic acetylcholine receptors (mAChRs) that may be activated by synaptically released acetylcholine during learning behaviors in vivo. Using acute hippocampal slices from the CA1 hippocampus of juvenile PV-GFP mice, we performed whole cell recordings from synaptically connected PV BC-CA1 pyramidal cell pairs to investigate how bath application of 10 μM muscarine impacts PPD and MPD at CA1 PV BC-pyramidal cell synapses. In accordance with previous studies, PPD and MPD magnitude increased with stimulation frequency. mAChR activation reduced IPSC amplitude and transiently reduced PPD, but MPD was largely maintained. Consistent with a reduction in release probability ( pr), MPD and mAChR activation increased both the coefficient of variation of IPSC amplitudes and the fraction of failures. Using variance-mean analysis, we converted MPD trains to pr functions and developed a kinetic model that optimally fit six distinct pr conditions. The model revealed that vesicular depletion caused MPD and that recovery from depression was dependent on calcium. mAChR activation reduced the presynaptic calcium transient fourfold and initial pr twofold, thereby reducing PPD. However, mAChR activation slowed calcium-dependent recovery from depression during sustained repetitive activity, thereby preserving MPD. Thus the activation of presynaptic mAChRs optimally protects PV BCs from vesicular depletion during short bursts of high-frequency activity.

Model of gradual phase shift of theta rhythm in the rat

1984 ◽  
Vol 52 (6) ◽  
pp. 1051-1065 ◽  
Author(s):  
L. W. Leung
Keyword(s):  
Phase Shift ◽  
Pyramidal Cell ◽  
Theta Rhythm ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Phase Reversal ◽  
Freely Moving Rats ◽  
Theta Frequency ◽  
Freely Moving ◽  
Somatic Inhibition

CA1 pyramidal cell is modeled by a linked series of passive compartments representing the soma and different parts of the dendritic tree. Intracellular postsynaptic potentials are simulated by conductance changes at one or more compartments. By assuming an infinite homogeneous extracellular medium and a particular geometrical arrangement of pyramidal cells, field potential profiles are generated from the current source-sinks of the compartments. The pyramidal cells are driven at the theta (theta)-frequency at different sites of the dendritic tree in order to simulate external driving of hippocampus by the septal cells. Inhibitory or excitatory driving at different sites gives extracellular dipole fields of different null zones and maxima. Phase reversal (180 degrees) of a dipole field generated by synchronous synaptic currents is completed within a depth of 150 micron. By driving two spatially distinct but overlapping dipole fields slightly phase-shifted (30-90 degrees) from each other, the resultant field shows a gradual phase shift of 180 degrees in over 400 micron depth and no (stationary) null zones. The latter field correspond to the theta-profiles seen in the freely moving rat. Somatic inhibition is proposed to be the synaptic process generating the theta-field potentials (named dipole I) in the urethananesthetized or curarized rat. Dipole I has amplitude maxima at the basal dendritic and the distal apical dendritic layers, with a distinct null zone and phase reversal at the apical side of the CA1 pyramidal cell layer. Rhythmic distal dendritic excitation, time-delayed to somatic inhibition, is proposed to be the additional dipole (dipole II) found in freely moving rats. The combination of dipoles I and II, phase-shifted from each other, causes the gradual theta-field phase shift. Experimental studies indicate that dipole I is atropine-sensitive and probably driven by a cholinergic septohippocampal input, whereas dipole II is atropine-resistant and may come from a pathway through both the septum and the entorhinal cortex. Variations of the phase profiles of the theta-field in freely moving rats by administration of anesthetic and cholinergic drugs and by normal changes in theta-frequency could be accounted for by the proposed model. Changes of the intracellular membrane potential, cellular firing rate, and evoked excitability at different phases of the theta-rhythm in anesthetized and freely moving rats can be predicted from the model, and they are in general agreement with the extant literature. In conclusion, theta-field is generated by a rhythmic somatic inhibition phase-shifted with a distal apical-dendritic excitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Intrinsic Ca2+-dependent theta oscillations in apical dendrites of hippocampal CA1 pyramidal cells in vitro

2014 ◽  
Vol 112 (3) ◽  
pp. 631-643 ◽  
Author(s):  
Allan Kjeldsen Hansen ◽  
Steen Nedergaard ◽  
Mogens Andreasen
Keyword(s):  
Frequency Band ◽  
Pyramidal Cells ◽  
Sine Wave ◽  
Detectable Effect ◽  
Ca1 Pyramidal Cells ◽  
Theta Frequency ◽  
Voltage Dependent ◽  
Oscillatory Mechanism ◽  
Apical Dendrites

Behavior-associated theta-frequency oscillation in the hippocampal network involves a patterned activation of place cells in the CA1, which can be accounted for by a somatic-dendritic interference model predicting the existence of an intrinsic dendritic oscillator. Here we describe an intrinsic oscillatory mechanism in apical dendrites of in vitro CA1 pyramidal cells, which is induced by suprathreshold depolarization and consists of rhythmic firing of slow spikes in the theta-frequency band. The incidence of slow spiking (29%) increased to 78% and 100% in the presence of the β-adrenergic agonist isoproterenol (2 μM) or 4-aminopyridine (2 mM), respectively. Prior depolarization facilitated the induction of slow spiking. Applied electrical field polarization revealed a distal dendritic origin of slow spikes. The oscillations were largely insensitive to tetrodotoxin, but blocked by nimodipine (10 μM), indicating that they depend on activation of L-type Ca2+ channels. Antagonists of T-, R-, N-, and P/Q-type Ca2+ channels had no detectable effect. The slow spike dimension and frequency was sensitive to 4-aminopyridine (0.1–2 mM) and TEA (10 mM), suggesting the contribution from voltage-dependent K+ channels to the oscillation mechanism. α-Dendrotoxin (10 μM), stromatoxin (2 μM), iberiotoxin (0.2 μM), apamin (0.5 μM), linorpidine (30 μM), and ZD7288 (20 μM) were without effect. Oscillations induced by sine-wave current injection or theta-burst synaptic stimulation were voltage-dependently attenuated by nimodipine, indicating an amplifying function of L-type Ca2+ channels on imposed signals. These results show that the apical dendrites have intrinsic oscillatory properties capable of generating rhythmic voltage fluctuations in the theta-frequency band.

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.

Plasticity in an electrosensory system. I. General features of a dynamic sensory filter

1996 ◽  
Vol 76 (4) ◽  
pp. 2483-2496 ◽  
Author(s):  
J. Bastian
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Cell ◽  
Electric Fish ◽  
Pyramidal Cells ◽  
Afferent Input ◽  
Firing Frequency ◽  
Negative Image ◽  
Local Stimulus ◽  
Adaptive Cancellation ◽  
Apical Dendrites

1. In this study we describe changes in neuronal responses within the primary electrosensory processing nucleus of a weakly electric fish that occur when the fish are exposed to repetitive patterns of electrosensory stimuli. Extracellular single-unit recordings show that pyramidal cells within the electrosensory lateral line lobe develop, over a time course of several minutes, an insensitivity to repetitive stimuli applied to a cell's receptive field (local stimulus). The pyramidal cell response cancellation only develops if the local stimulus is applied simultaneously with a diffuse pattern of electrosensory stimulation that affects the entire fish, or with proprioceptive stimuli. 2. The mechanism by which responses to repetitive afferent inputs are canceled relies on the central generation of "negative image inputs" that provide increased inhibitory input to a cell's apical dendrites at times when excitatory afferent input is increased. The negative image input becomes excitatory when afferent excitation is reduced or when input from inhibitory interneurons is predominant. The integration of a specific pattern of receptor afferent input with the complementary negative image input results in strong attenuation of pyramidal cell responses. The negative image inputs are plastic, so that a single pyramidal cell can learn to reject a variety of afferent input patterns. 3. These electric fish commonly experience repetitive electrosensory signals as a result of changes in posture. Because the electric organ is located in the trunk and tail, cyclical movements associated with exploratory behaviors result in amplitude modulations (AMs) of the electric field, and these AMs alter electroreceptor afferent firing frequency but not the firing frequency of second-order pyramidal cells. The adaptive cancellation mechanism described in this study can account for the insensitivity of pyramidal cells to reafferent electrosensory stimulation caused by tail movements and other postural changes. 4. The tail movements generate proprioceptive as well as electrosensory inputs, and either of these signals alone provides sufficient information for the generation of negative image inputs. The size of the negative image is larger, however, if both inputs are active. 5. The synaptic plasticity underlying the development of negative image inputs has a long-term component; under appropriate conditions changes in synaptic efficacy persist for > 30 min. 6. Normally functioning glutamatergic synapses are necessary for the expression of the synaptic plasticity associated with this cancellation mechanism. The development of negative image responses is blocked by micropressure ejection of the glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione into the neighborhood of the pyramidal cell apical dendrites. 7. The adaptive cancellation of repetitive inputs is based on anti-Hebbian mechanisms; that is, correlated pre- and postsynaptic activity lead to a reduction in the excitatory input provided by the plastic synapses. As has been shown for several other systems, the cancellation mechanism reduces the cells responses to reafferent patterns of sensory input. In addition, the results of this study indicate that the mechanism may be more general, enabling the system to also cancel patterns of input resulting from exogenous stimuli.

Intrinsic and Synaptic Mechanisms Determining the Timing of Neuron Population Activity During Hippocampal Theta Oscillation

2006 ◽  
Vol 96 (6) ◽  
pp. 2889-2904 ◽  
Author(s):  
Gergő Orbán ◽  
Tamás Kiss ◽  
Péter Érdi
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Cells ◽  
Neuron Population ◽  
Population Activity ◽  
Theta Oscillation ◽  
Hippocampal Ca1 ◽  
Theta Frequency ◽  
Hippocampal Theta

Hippocampal theta (3–8 Hz) is a major electrophysiological activity in rodents, which can be found in primates and humans as well. During theta activity, pyramidal cells and different classes of interneurons were shown to discharge at different phases of the extracellular theta. A recent in vitro study has shown that theta-frequency oscillation can be elicited in a hippocampal CA1 slice by the activation of metabotropic glutamate receptors with similar pharmacological and physiological profile that was found in vivo. We constructed a conductance based three-population network model of the hippocampal CA1 region to study the specific roles of neuron types in the generation of the in vitro theta oscillation and the emergent network properties. Interactions between pairs of neuron populations were studied systematically to assess synchronization and delay properties. We showed that the circuitry consisting of pyramidal cells and two types of hippocampal interneurons [basket and oriens lacunosum-moleculare (O-LM) neurons] was able to generate coherent theta-frequency population oscillation. Furthermore, we found that hyperpolarization-activated nonspecific cation current in pyramidal cells, but not in O-LM neurons, plays an important role in the timing of spike generation, and thus synchronization of pyramidal cells. The model was shown to exhibit the same phase differences between neuron population activities found in vivo, supporting the idea that these patterns of activity are determined internal to the hippocampus.

Function of NMDA Receptors and Persistent Sodium Channels in a Feedback Pathway of the Electrosensory System

2001 ◽  
Vol 86 (4) ◽  
pp. 1612-1621 ◽  
Author(s):  
Neil Berman ◽  
Robert J. Dunn ◽  
Leonard Maler
Keyword(s):  
Nmda Receptors ◽  
Sodium Channels ◽  
Pyramidal Cell ◽  
Voltage Dependence ◽  
Late Phase ◽  
Pyramidal Cells ◽  
Receptor Component ◽  
Voltage Dependent ◽  
Gymnotiform Fish ◽  
Apical Dendrites

Voltage-dependent amplification of ionotropic glutamatergic excitatory postsynaptic potentials (EPSPs) can, in many vertebrate neurons, be due either to the intrinsic voltage dependence of N-methyl-d-aspartate (NMDA) receptors, or voltage-dependent persistent sodium channels expressed on postsynaptic dendrites or somata. In the electrosensory lateral line lobe (ELL) of the gymnotiform fish Apteronotus leptorhynchus,glutamatergic inputs onto pyramidal cell apical dendrites provide a system where both amplification mechanisms are possible. We have now examined the roles for both NMDA receptors and sodium channels in the control of EPSP amplitude at these synapses. An antibody specific for the A. leptorhynchus NR1 subunit reacted strongly with ELL pyramidal cells and were particularly abundant in the spines of pyramidal cell apical dendrites. We have also shown that NMDA receptors contributed strongly to the late phase of EPSPs evoked by stimulation of the feedback fibers terminating on the apical dendritic spines; further, these EPSPs were voltage dependent. Blockade of NMDA receptors did not, however, eliminate the voltage dependence of these EPSPs. Blockade of somatic sodium channels by local somatic ejection of tetrodotoxin (TTX), or inclusion of QX314 (an intracellular sodium channel blocker) in the recording pipette, reduced the evoked EPSPs and completely eliminated their voltage dependence. We therefore conclude that, in the subthreshold range, persistent sodium currents are the main contributor to voltage-dependent boosting of EPSPs, even when they have a large NMDA receptor component.

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