Controlling Synaptic Input Patterns In Vitro by Dynamic Photo Stimulation

2005 ◽  
Vol 94 (4) ◽  
pp. 2948-2958 ◽  
Author(s):  
Clemens Boucsein ◽  
Martin Nawrot ◽  
Stefan Rotter ◽  
Ad Aertsen ◽  
Detlef Heck
Keyword(s):  
Synaptic Input ◽  
Laser Scanning ◽  
Temporal Structure ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Network Activity ◽  
Scanning System ◽  
Single Neurons

Recent experimental and theoretical work indicates that both the intensity and the temporal structure of synaptic activity strongly modulate the integrative properties of single neurons in the intact brain. However, studying these effects experimentally is complicated by the fact that, in experimental systems, network activity is either absent, as in the acute slice preparation, or difficult to monitor and to control, as in in vivo recordings. Here, we present a new implementation of neurotransmitter uncaging in acute brain slices that uses functional projections to generate tightly controlled, spatio-temporally structured synaptic input patterns in individual neurons. For that, a set of presynaptic neurons is activated in a precisely timed sequence through focal photolytic release of caged glutamate with the help of a fast laser scanning system. Integration of synaptic inputs can be studied in postsynaptic neurons that are not directly stimulated with the laser, but receive input from the targeted neurons through intact axonal projections. Our new approach of dynamic photo stimulation employs functional synapses, accounts for their spatial distribution on the dendrites, and thus allows study of the integrative properties of single neurons with physiologically realistic input. Data obtained with our new technique suggest that, not only the neuronal spike generator, but also synaptic transmission and dendritic integration in neocortical pyramidal cells, can be highly reliable.

Reduction of Zolpidem Sensitivity in a Freeze Lesion Model of Neocortical Dysgenesis

1999 ◽  
Vol 81 (1) ◽  
pp. 404-407 ◽  
Author(s):  
R. Anthony Defazio ◽  
John J. Hablitz
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Benzodiazepine Receptor ◽  
Decay Time Constant ◽  
Α Subunit ◽  
Rat Neocortex

DeFazio, R. Anthony and John J. Hablitz. Reduction of zolpidem sensitivity in a freeze lesion model of neocortical dysgenesis. J. Neurophysiol. 81: 404–407, 1999. Early postnatal freeze lesions in rat neocortex produce anatomic abnormalities resembling those observed in human patients with seizure disorders. Although in vitro brain slices containing the lesion are hyperexcitable, the mechanisms of this alteration have yet to be elucidated. To test the hypothesis that changes in postsynaptic inhibitory receptors may underlie this hyperexcitability, we examined properties of γ-aminobutyric acid type A receptor (GABAAR)–mediated miniature inhibitory postsynaptic currents (mIPSCs). Recordings were obtained in layer II/III pyramidal cells located 1–2 mm lateral to the lesion. mIPSC peak amplitude and rate of rise were increased relative to nonlesioned animals, whereas decay time constant and interevent interval were unaltered. Bath application of zolpidem at a concentration (20 nM) specific for activation of the type 1 benzodiazepine receptor had no significant effect on decay time constant in six of nine cells. Exposure to higher concentrations (100 nM) enhanced the decay time constant of all cells tested ( n = 7). Because mIPSCs from unlesioned animals were sensitive to both concentrations of zolpidem, these results suggest that freeze lesions may decrease the affinity of pyramidal cell GABAARs for zolpidem. This could be mediated via a change in α-subunit composition of the GABAAR, which eliminates the type 1 benzodiazepine receptor.

Spike Timing of Lacunosom-Moleculare Targeting Interneurons and CA3 Pyramidal Cells During High-Frequency Network Oscillations In Vitro

2007 ◽  
Vol 98 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Jay Spampanato ◽  
Istvan Mody
Keyword(s):  
High Frequency ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Spike Timing ◽  
Network Activity ◽  
Network Oscillations ◽  
Ca3 Pyramidal Cells

Network activity in the 200- to 600-Hz range termed high-frequency oscillations (HFOs) has been detected in epileptic tissue from both humans and rodents and may underlie the mechanism of epileptogenesis in experimental rodent models. Slower network oscillations including theta and gamma oscillations as well as ripples are generated by the complex spike timing and interactions between interneurons and pyramidal cells of the hippocampus. We determined the activity of CA3 pyramidal cells, stratum oriens lacunosum-moleculare (O-LM) and s. radiatum lacunosum-moleculare (R-LM) interneurons during HFO in the in vitro low-Mg2+ model of epileptiform activity in GIN mice. In these animals, interneurons can be identified prior to cell-attached recordings by the expression of green-fluorescent protein (GFP). Simultaneous local field potential recordings from s. pyramidale and on-cell recordings of individual interneurons and principal cells revealed three primary firing behaviors of the active cells: 36% of O-LM interneurons and 60% of pyramidal cells fired action potentials at high frequencies during the HFO. R-LM interneurons were biphasic in that they fired at high frequency at the beginning of the HFO but stopped firing before its end. When considering only the highest frequency component of the oscillations most pyramidal cells fired on the rising phase of the oscillation. These data provide evidence for functional distinction during HFOs within otherwise homogeneous groups of O-LM interneurons and pyramidal cells.

scholarly journals Dopaminergic Modulation of Local Network Activity in Rat Prefrontal Cortex

2007 ◽  
Vol 97 (6) ◽  
pp. 4120-4128 ◽  
Author(s):  
Susanta Bandyopadhyay ◽  
John J. Hablitz
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Receptor Agonist ◽  
Neuronal Networks ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Lateral Spread ◽  
Local Network ◽  
Evoked Activity

Dopamine modulates prefrontal cortex excitability in complex ways. Dopamine's net effect on local neuronal networks is therefore difficult to predict based on studies on pharmacologically isolated excitatory or inhibitory connections. In the present work, we have studied the effects of dopamine on evoked activity in acute rat brain slices when both excitation and inhibition are intact. Whole cell recordings from layer II/III pyramidal cells under conditions of normal synaptic transmission showed that bath-applied dopamine (30 μM) increased the outward inhibitory component of composite postsynaptic currents, whereas inward excitatory currents were not significantly affected. Optical imaging with the voltage-sensitive dye N-(3-(triethylammonium)propyl)-4-(4-(p-diethylaminophenyl)buta-dienyl)pyridinium dibromide revealed that bath application of dopamine significantly decreased the amplitude, duration, and lateral spread of activity in local cortical networks. This effect of dopamine was observed both with single and train (5 at 20 Hz) stimuli. The effect was mimicked by the D1-like receptor agonist R(+)-6-chloro-7,8-dihydroxy-1-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1 μM) and was blocked by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (10 μM), a selective antagonist for D1-like receptors. The D2-like receptor agonist quinpirole (10 μM) had no significant effect on evoked dye signals. Our results suggest that dopamine's effect on inhibition dominates over that on excitation under conditions of normal synaptic transmission. Such neuromodulation by dopamine may be important for maintenance of stability in local neuronal networks in the prefrontal cortex.

Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings

2007 ◽  
Vol 97 (1) ◽  
pp. 746-760 ◽  
Author(s):  
Yousheng Shu ◽  
Alvaro Duque ◽  
Yuguo Yu ◽  
Bilal Haider ◽  
David A. McCormick
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Initial Segment ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Up States ◽  
Action Potential Initiation ◽  
Potential Initiation

Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole cell recordings from the soma and axon or soma and apical dendrite of layer 5 pyramidal neurons during normal recurrent network activity (up states), the intrasomatic or intradendritic injection of artificial synaptic barrages, and during epileptiform discharges in vitro. We demonstrate that under all of these conditions, the real or artificial synaptic bombardments propagate through the dendrosomatic-axonal arbor and consistently initiate action potentials in the axon initial segment that then propagate to other parts of the cell. Action potentials recorded intracellularly in vivo during up states and in response to visual stimulation exhibit properties indicating that they are typically initiated in the axon. Intracortical axons were particularly well suited to faithfully follow the generation of action potentials by the axon initial segment. Action-potential generation was more reliable in the distal axon than at the soma during epileptiform activity. These results indicate that the axon is the preferred site of action-potential initiation in cortical pyramidal cells, both in vivo and in vitro, with state-dependent back propagation through the somatic and dendritic compartments.

scholarly journals Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network development in vivo

2020 ◽  
Author(s):  
Jürgen Graf ◽  
Chuanqiang Zhang ◽  
Stephan Lawrence Marguet ◽  
Tanja Herrmann ◽  
Tom Flossmann ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Network Dynamics ◽  
Brain Slices ◽  
Network Activity ◽  
Long Term Effects ◽  
Network Function ◽  
Excitatory Gaba ◽  
A Minor

AbstractNKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in-vitro excitatory GABA actions and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics and behavioral performance are subtle. Our data reveal a neural network function of depolarizing GABA in the hippocampus in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.

scholarly journals Regional heterogeneity of developing GABAergic interneuron excitation in vivo

2019 ◽  
Author(s):  
Yasunobu Murata ◽  
Matthew T. Colonnese
Keyword(s):  
Synapse Formation ◽  
Critical Role ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Intact Brain

AbstractGABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are indeed excitatory in hippocampus at postnatal-day 3 (P3), and responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas cortical interneurons are inhibitory at P3 and remain so throughout development. This regional and age heterogeneity is the result of a change in chloride reversal potential as activation of light-gated anion channels expressed in glutamatergic neurons causes firing in hippocampus at P3, but silences it at P7. This study in the intact brain reveals a critical role for GABAergic interneuron excitation in neonatal hippocampus, and a surprising heterogeneity of interneuron function in cortical circuits that was not predicted from in vitro studies.

scholarly journals Dopamine modulates excitatory transmission to orexin neurons in a receptor subtype-specific manner

2019 ◽  
Vol 316 (1) ◽  
pp. R68-R75 ◽  
Author(s):  
Victoria Linehan ◽  
Todd M. Rowe ◽  
Michiru Hirasawa
Keyword(s):  
Receptor Antagonist ◽  
Sch 23390 ◽  
Brain Slices ◽  
Cellular Mechanism ◽  
Synaptic Activity ◽  
Network Activity ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Excitatory Transmission ◽  
Dopaminergic Modulation

Dopamine (DA) can promote or inhibit consummatory and reward-related behaviors by activating different receptor subtypes in the lateral hypothalamus and perifornical area (LH/PF). Because orexin neurons are involved in reward and localized in the LH/PF, DA may modulate these neurons to influence reward-related behaviors. To determine the cellular mechanism underlying dopaminergic modulation of orexin neurons, the effect of DA on excitatory transmission to these neurons was investigated using in vitro electrophysiology on rat brain slices. We found that low concentrations (0.1–1 µM) of DA increased evoked excitatory postsynaptic current amplitude while decreasing paired-pulse ratio. In contrast, high concentrations (10–100 µM) of DA did the opposite. The excitatory effect of low DA was blocked by the D1 receptor antagonist SCH-23390, whereas the inhibitory effect of high DA was blocked by the D2 receptor antagonist sulpiride. These results indicate distinct roles of D1 and D2 receptors in bidirectional presynaptic modulation of excitatory transmission. DA had stronger effects on isolated synaptic activity than repetitive ones, suggesting that sensitivity to dopaminergic modulation depends on the level of network activity. In orexin neurons from high-fat diet-fed rats, a high concentration of DA was less effective in suppressing repetitive synaptic activity compared with chow controls. Therefore, in diet-induced obesity, intense synaptic inputs may preferentially reach orexin neurons while intermittent signals are inhibited by high DA levels. In summary, our study provides a cellular mechanism by which DA may exert opposite behavioral effects in the LH/PF through bidirectional modulation of orexin neurons via different DA receptors.

scholarly journals Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Nicola H. Morgan ◽  
Ian M. Stanford ◽  
Gavin L. Woodhall
Keyword(s):  
Synaptic Transmission ◽  
Cannabinoid Receptors ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Gabaergic Neurotransmission ◽  
Network Oscillations ◽  
Gabaergic Synaptic Transmission

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M), an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Regular oscillations of synaptic activity in spinal networks in vitro

1993 ◽  
Vol 70 (3) ◽  
pp. 871-878 ◽  
Author(s):  
J. Streit
Keyword(s):  
Spinal Cord ◽  
Excitatory Amino Acid ◽  
Temporal Structure ◽  
Activity Patterns ◽  
Nmda Antagonist ◽  
Synaptic Activity ◽  
Burst Length ◽  
Organotypic Slice Cultures ◽  
Random Patterns

1. Spontaneous synaptic potentials were recorded in motoneurons grown in organotypic slice cultures of embryonic rat spinal cord. In 71 of 85 cells these potentials appeared without obvious temporal structure (random patterns); in the remaining 14 cells they appeared in bursts (rhythmic patterns). 2. Random activity patterns could be converted into rhythmic patterns by treating the cultures with strychnine, bicuculline, or both. The excitatory amino acid N-methyl-D-aspartate (NMDA) transiently increased the rate of spontaneous synaptic activity without inducing rhythmic patterns. The NMDA antagonist 7-chloro-kynurenate reduced the burst rate while leaving the burst length unchanged in rhythmic patterns. In random patterns it reduced the rate of spontaneous synaptic activity by 68%. 3. Histograms of interevent times of the random patterns were best fitted by the sum of two expontentials, suggesting that the random type of activity could not be described simply as a Poisson process but involved at least one additional mechanism. 4. Rhythmic patterns consisted of bursts of activity with a mean burst length of 2.2 s that were separated by interburst intervals with a mean length of 6.6 s. Within the bursts autocorrelograms revealed regular oscillations with a mean period of 226 ms in 6 of 11 experiments with rhythmic patterns. The period showed little variation between individual experiments (202-288 ms). In random patterns no oscillations were detected. 5. Within the spontaneous bursts the excitatory postsynaptic potentials (EPSPs) progressively declined in amplitude. A corresponding depression of EPSPs was observed when trains of electrical stimuli were applied at 5 Hz to the dorsal horns of the spinal cord slices.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ernesto Flores-Martínez ◽  
Fernando Peña-Ortega
Keyword(s):  
Prefrontal Cortex ◽  
Brain Slices ◽  
Amyloid Β ◽  
Network Activity ◽  
Amyloid Β Peptide ◽  
Cell Level ◽  
Long Range Interactions ◽  
Induced Changes ◽  
The Brain

Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer Disease (AD). Considering that these malfunctions correlate with the increase in the brain’s amyloid beta (Aβ) peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain.

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