scholarly journals Tonic GABA ‐activated synaptic and extrasynaptic currents in dentate gyrus granule cells and CA3 pyramidal neurons along the mouse hippocampal dorsoventral axis

Hippocampus ◽  
2020 ◽  
Vol 30 (11) ◽  
pp. 1146-1157
Author(s):  
Olga Netsyk ◽  
Hayma Hammoud ◽  
Sergiy V. Korol ◽  
Zhe Jin ◽  
Atieh S. Tafreshiha ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Dorsoventral Axis ◽  
Ca3 Pyramidal Neurons

Complex Synaptic Current Waveforms Evoked in Hippocampal Pyramidal Neurons by Extracellular Stimulation of Dentate Gyrus

1998 ◽  
Vol 79 (5) ◽  
pp. 2475-2484 ◽  
Author(s):  
Zixiu Xiang ◽  
Thomas H. Brown
Keyword(s):  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Functional Anatomy ◽  
Granule Cell Layer ◽  
Synaptic Current ◽  
Bathing Medium ◽  
Hippocampal Pyramidal Neurons ◽  
Ca3 Pyramidal Neurons ◽  
Stimulation Of

Xiang, Zixiu and Thomas H. Brown. Complex synaptic current waveforms evoked in hippocampal pyramidal neurons by extracellular stimulation of dentate gyrus. J. Neurophysiol. 79: 2475–2484, 1998. Excitatory postsynaptic currents (EPSCs) evoked in hippocampal CA3 pyramidal neurons by extracellular stimulation of the dentate gyrus typically exhibit complex waveforms. They commonly have inflections or notches on the rising phase; the decay phase may exhibit notches or other obvious departures from a simple monoexponential decline; they often display considerable variability in the latency from stimulation to the peak current; and the rise times tend to be long. One hypothesis is that these complex EPSC waveforms might result from excitation via other CA3 pyramidal cells that were recruited antidromically or trans-synaptically by the stimulus due to the complex anatomy of this region. An alternative hypothesis is that EPSC complexity does not emerge from the functional anatomy but rather reflects an unusual physiological property, intrinsic to excitation-secretion coupling in mossy-fiber (mf) synaptic terminals, that causes asynchronous quantal release. We evaluated certain predictions of our anatomic hypothesis by adding a pharmacological agent to the normal bathing medium that should suppress di- or polysynaptic responses. For this purpose we used baclofen (3 μM), a selective agonist for the γ-aminobutyric acid B receptor. The idea was that baclophen should discriminate against polysynaptic versus monosynaptic inputs by hyperpolarizing the cells, bringing them further from spike threshold and possibly also through inhibitory presynaptic actions. Whole cell recordings were done from visually preselected CA3 pyramidal neurons and EPSCs were evoked by fine bipolar electrodes positioned into the granule cell layer of the dentate. To the extent that the EPSC complexity reflects di- or polysynaptic responses, we predicted baclofen to reduce the number of notches on the rising and decay phases, reduce the variance in latency to peak of the EPSCs, decrease the amplitudes and rise times of the individual and averaged EPSCs, and increase the apparent failures in evoked EPSCs. All of these predictions were confirmed, in support of the hypothesis that these complex EPSC waveforms commonly reflect di- or polysynaptic responses. We also documented a distinctly different, intermittent, form of EPSC complexity, which also is predicted and easily explained by our anatomic hypothesis. In particular, the results were in accord with the suggestion that stimulation of the dentate gyrus might antidromically stimulate axon collaterals of CA3 neurons that make recurrent synapses onto the recorded cell. We conclude that the overall pattern of results is consistent with expectations based on the functional anatomy. The explanation does not demand a special type of intrinsic asynchronous mechanism for excitation-secretion coupling in the mf synapses.

Inhibitory role of dentate hilus neurons in guinea pig hippocampal slice

1990 ◽  
Vol 64 (1) ◽  
pp. 46-56 ◽  
Author(s):  
W. Muller ◽  
U. Misgeld
Keyword(s):  
Guinea Pig ◽  
Dentate Gyrus ◽  
Hippocampal Slice ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Stratum Pyramidale ◽  
Stratum Oriens ◽  
Bath Application ◽  
Ca3 Neurons ◽  
Hilar Neurons

1. Current and voltage-clamp recording of CA3/CA4 pyramidal neurons, hilar neurons, and granule cells or pairs of these neurons were used to study the generation of Cl-dependent and K-dependent inhibitory postsynaptic potentials (IPSPs) in the guinea pig hippocampal slice preparation. 2. A sequence of an early Cl-dependent and a late K-dependent IPSP was evoked in CA3 neurons by electrical stimulation from the stratum moleculare of the dentate gyrus, the hilus, and the stratum oriens/alveus. Blockade of glutamatergic excitation by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)-2-amino-5-phosphonovaleric acid (APV, 30 microM) abolished IPSPs evoked from the stratum moleculare of the dentate gyrus, but IPSPs could still be evoked from the hilus and the stratum oriens/alveus. 3. Repetitive giant IPSPs, which consisted of Cl-dependent and K-dependent components, were evoked by bath application of 4-aminopyridine (4-AP, 10-50 microM) in CA3 neurons and in granule cells. Giant IPSPs were blocked by bath-applied tetrodotoxin (TTX). In addition, 4-AP hyperpolarized CA3 neurons in a Cl-dependent and picrotoxin-sensitive way. 4. Focal application of TTX to the dentate gyrus or the hilus considerably reduced the amplitude of giant IPSPs evoked by 4-AP in CA3 neurons. In hilar neurons, 4-AP evoked repetitive bursts, eventually, but not necessarily intermingled with giant IPSPs. Bursts were observed in hilar neurons in presence as well as absence of CNQX and APV. 5. In paired recordings, bursts in hilar neurons induced by 4-AP occurred simultaneously to giant IPSPs in granule cells and CA3 neurons, and giant IPSPs in granule cells occurred simultaneously to giant IPSPs in CA3 neurons. Blockade of glutamatergic excitation by CNQX and APV did not abolish this synchrony. 6. 4-AP-evoked Cl- and K-dependent IPSPs were, unlike electrically evoked IPSPs, not strictly coupled: some 20% of large IPSPs and up to 90% of small IPSPs were either Cl or K dependent. In granule cells K-dependent components either preceded or followed Cl-dependent components. 7. K-dependent IPSPs only could be evoked in CA3 neurons by focal application of 4-AP (1 mM) to the hilus, the stratum lacunosum moleculare or the stratum pyramidale. Wash out of Ca for 15–20 min blocked the Cl-dependent but not the K-dependent component of giant IPSPs evoked by bath-applied 4-AP.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Changes in Mint1, a Novel Synaptic Protein, After Transient Global Ischemia in Mouse Hippocampus

2000 ◽  
Vol 20 (10) ◽  
pp. 1437-1445 ◽  
Author(s):  
Hiroyuki Nishimura ◽  
Tomohiro Matsuyama ◽  
Kyoko Obata ◽  
Yatsuka Nakajima ◽  
Hideto Kitano ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Vesicle ◽  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Global Ischemia ◽  
Mouse Hippocampus ◽  
Ca3 Pyramidal Neurons ◽  
Neuronal Transmission ◽  
Transient Global Ischemia

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is involved in synaptic vesicle exocytosis. Its potential effects on development of ischemic damage to neurons have not yet been evaluated. The authors examined changes in mint1 and other synaptic proteins by immunohistochemistry after transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhinal cortex to the hippocampus and in the mossy fibers linking the granule cells of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partner of mint1, was distributed uniformly throughout the hippocampus, and synaptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibers. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enhancement at 3 days. However, munc18-1 and synaptophysin 2 were substantially expressed in the same region throughout the reperfusion period. These findings suggest that mint1 participates in neuronal transmission along the excitatory pathway linking the entorhinal cortex to CA3 in the hippocampus. Because mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delayed neuronal death.

scholarly journals Melatonin Influences Structural Plasticity in the Axons of Granule Cells in the Dentate Gyrus of Balb/C Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 73 ◽  
Author(s):  
Gerardo Ramírez-Rodríguez ◽  
Sandra Olvera-Hernández ◽  
Nelly Vega-Rivera ◽  
Leonardo Ortiz-López
Keyword(s):  
Dentate Gyrus ◽  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Structural Plasticity ◽  
Granular Cell ◽  
Newborn Neurons ◽  
The Impact ◽  
Ca3 Region

Melatonin, the main product synthesized by the pineal gland, acts as a regulator of the generation of new neurons in the dentate gyrus (DG). Newborn neurons buffer the deleterious effects of stress and are involved in learning and memory processes. Furthermore, melatonin, through the regulation of the cytoskeleton, favors dendrite maturation of newborn neurons. Moreover, newborn neurons send their axons via the mossy fiber tract to Cornu Ammonis 3 (CA3) region to form synapses with pyramidal neurons. Thus, axons of newborn cells contribute to the mossy fiber projection and their plasticity correlates with better performance in several behavioral tasks. Thus, in this study, we analyzed the impact of exogenous melatonin (8 mg/kg) administered daily for one- or six-months on the structural plasticity of infrapyramidal- and suprapyramidal mossy fiber projection of granule cells in the DG in male Balb/C mice. We analyzed the mossy fiber projection through the staining of calbindin, that is a calcium-binding protein localized in dendrites and axons. We first found an increase in the number of calbindin-positive cells in the granular cell layer in the DG (11%, 33%) after treatment. Futhermore, we found an increase in the volume of suprapyramidal (>135%, 59%) and infrapyramidal (>128%, 36%) mossy fiber projection of granule neurons in the DG after treatment. We also found an increase in the volume of CA3 region (>146%, 33%) after treatment, suggesting that melatonin modulates the structural plasticity of the mossy fiber projection to establish functional synapses in the hippocampus. Together, the data suggest that, in addition to the previously reported effects of melatonin on the generation of new neurons and its antidepressant like effects, melatonin also modulates the structural plasticity of axons in granule cells in the DG.

scholarly journals An optogenetic method for investigating presynaptic molecular regulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuni Kay ◽  
Bruce E. Herring
Keyword(s):  
Pyramidal Neurons ◽  
Molecular Regulation ◽  
Glutamatergic Synapses ◽  
Experimental Conditions ◽  
Regulatory Pathways ◽  
Genetic Manipulations ◽  
Postsynaptic Protein ◽  
Presynaptic Function ◽  
Synaptotagmin 1 ◽  
Ca3 Pyramidal Neurons

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

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