scholarly journals Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

2019 ◽  
Author(s):  
Poonam Mishra ◽  
Rishikesh Narayanan
Keyword(s):  
Dentate Gyrus ◽  
Temporal Summation ◽  
Granule Cells ◽  
Neuronal Morphology ◽  
Intrinsic Excitability ◽  
Activity Levels ◽  
Frequency Dependent ◽  
Information Encoding ◽  
Response Properties ◽  
Electrophysiological Properties

ABSTRACTThe dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely the suprapyramidal blade, the crest region and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole-cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents, and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies, voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly less action potentials compared to those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information, and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing.

scholarly journals Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

2020 ◽  
Vol 123 (2) ◽  
pp. 755-772 ◽  
Author(s):  
Poonam Mishra ◽  
Rishikesh Narayanan
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Temporal Summation ◽  
Granule Cells ◽  
Intrinsic Excitability ◽  
Frequency Dependent ◽  
Response Properties ◽  
Whole Cell Patch Clamp ◽  
Afferent Information

The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest region, and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns, and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies and voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly fewer action potentials compared with those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing. NEW & NOTEWORTHY We employed whole cell patch-clamp recordings from granule cells in the three subregions of the rat dentate gyrus to demonstrate considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, granule cells did not express membrane potential resonance, and their impedance profiles lacked inductive phase leads at all measured frequencies. Our analyses also show that granule cells manifest class I excitability characteristics, categorizing them as integrators of afferent information.

scholarly journals Dentate gyrus somatostatin cells are required for contextual discrimination during episodic memory encoding

2019 ◽  
Author(s):  
Cristian Morales ◽  
Juan Facundo Morici ◽  
Nelson Espinosa ◽  
Agostina Sacson ◽  
Ariel Lara-Vasquez ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Molecular Layer ◽  
Memory Systems ◽  
Pattern Separation ◽  
Activity Levels ◽  
Memory Encoding ◽  
Somatostatin Cells ◽  
Somatostatin Neurons

AbstractEpisodic memory establishes and stores relations among the different elements of an experience, which are often similar and difficult to distinguish. Pattern separation, implemented by the dentate gyrus, is a neural mechanism that allows the discrimination of similar experiences by orthogonalizing synaptic inputs. Granule cells support such disambiguation by sparse rate coding, a process tightly controlled by highly diversified GABAergic neuronal populations, such as somatostatin-expressing cells which directly target the dendritic arbor of granule cells, massively innervated by entorhinal inputs reaching the molecular layer and conveying contextual information. Here, we tested the hypothesis that somatostatin neurons regulate the excitability of the dentate gyrus, thus controlling the efficacy of pattern separation during memory encoding in mice. Indeed, optogenetic suppression of dentate gyrus somatostatin neurons increased spiking activity in putative excitatory neurons and triggered dentate spikes. Moreover, optical inhibition of somatostatin neurons impaired both contextual and spatial discrimination of overlapping episodic-like memories during task acquisition. Importantly, effects were specific for similar environments, suggesting that pattern separation was selectively engaged when overlapping conditions ought to be distinguished. Overall, our results suggest that somatostatin cells regulate excitability in the dentate gyrus and are required for effective pattern separation during episodic memory encoding.Significance statementMemory systems must be able to discriminate stored representations of similar experiences in order to efficiently guide future decisions. This is solved by pattern separation, implemented in the dentate gyrus by granule cells to support episodic memory formation. The tonic inhibitory bombardment produced by multiple GABAergic cell populations maintains low activity levels in granule cells, permitting the process of pattern separation. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the dentate gyrus. Hence, somatostatin cells constitute an ideal candidate to regulate pattern separation. Here, by using optogenetic stimulation in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.

scholarly journals Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

2021 ◽  
Author(s):  
Sameera Shridhar ◽  
Poonam Mishra ◽  
Rishikesh Narayanan
Keyword(s):  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Granule Cells ◽  
Dominant Role ◽  
Activity Patterns ◽  
Brain Regions ◽  
Intrinsic Excitability ◽  
Context Specific ◽  
Structural Heterogeneities ◽  
Strong Relationships

ABSTRACTNeurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic, unbiased, and physiologically constrained search to identify the mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneous plasticity profiles obtained with two different induction protocols. However, prior predictions about strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult-neurogenesis-induced structural heterogeneities were accounted for. Strikingly, despite the concomitant expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable through synergistic interactions among these heterogeneities. Importantly, consequent to strong relationships with intrinsic excitability measurements, we found that synaptic plasticity in the physiological range was achieved in immature cells despite their electrophysiologically-observed weak synaptic strengths. Together, our analyses unveil the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. Broadly, these analyses emphasize that the mechanistic origins of and the implications for plasticity heterogeneities need quantitative characterization across brain regions, particularly focusing on context-specific encoding of learned behavior.

scholarly journals Dentate Gyrus Somatostatin Cells are Required for Contextual Discrimination During Episodic Memory Encoding

2020 ◽  
Author(s):  
Cristian Morales ◽  
Juan Facundo Morici ◽  
Nelson Espinosa ◽  
Agostina Sacson ◽  
Ariel Lara-Vasquez ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Memory Systems ◽  
Pattern Separation ◽  
Activity Levels ◽  
Connection Probability ◽  
Somatostatin Cells ◽  
Formation Pattern

Abstract Memory systems ought to store and discriminate representations of similar experiences in order to efficiently guide future decisions. This problem is solved by pattern separation, implemented in the dentate gyrus (DG) by granule cells to support episodic memory formation. Pattern separation is enabled by tonic inhibitory bombardment generated by multiple GABAergic cell populations that strictly maintain low activity levels in granule cells. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the DG. Nonetheless, somatostatin cells have very low connection probability and synaptic efficacy with both granule cells and other interneuron types. Hence, the role of somatostatin cells in DG circuitry, particularly in the context of pattern separation, remains uncertain. Here, by using optogenetic stimulation and behavioral tasks in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.

scholarly journals Inhibition of Hepatic Acyl Coa Oxidase 1 (ACOX1), A Peroxisome Β-Oxidation Enzyme, Modifies Brain Fatty Acid Profile And Intrinsic Membrane Properties in Granule Cells of Rat Dentate Gyrus

2021 ◽  
pp. 1-23
Author(s):  
Fereshteh Motamedi ◽  
◽  
Fariba Khodagholi ◽  
Leila Dargahi ◽  
Hamid Gholami Pourbadie ◽  
...  
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Dentate Gyrus ◽  
Fatty Acid Profile ◽  
Acid Composition ◽  
Granule Cells ◽  
Membrane Properties ◽  
Electrophysiological Properties ◽  
The Brain ◽  
Oxidation Enzyme

Peroxisomes are the essential organelles in lipid metabolism. They contain enzymes for β-oxidation of very-long-chain fatty acids, which cannot break down in mitochondria. A reduced expression in hepatic Acyl-CoA oxidase1 (ACOX1), a peroxisome β-oxidation enzyme, followed by modification of the brain fatty acid profile has been seen in aged rodents. These studies have suggested a potential role for peroxisome β-oxidation in brain aging. This study was designed to examine the effect of hepatic ACOX1 inhibition on brain fatty acid composition and neuronal cell activities of young rats (200-250 g). A specific ACOX1 inhibitor, 10, 12- tricosadiynoic acid (TDYA), 100 μg/kg (in olive oil) was given by daily gavage administration for 25 days in male Wistar rats. The brain fatty acid composition and electrophysiological properties of dentate gyrus granule cells were determined by gas chromatography and whole-cell patch-clamp, respectively. A significant increase in C20, C22, C18:1, C20:1, and a decrease of C18, C24, C20:3n6 and C22:6n3 were found in TDYA treated rats compared to the control group. The results show that ACOX1 inhibition changes fatty acid composition similar to old rats. ACOX1 inhibition caused hyperpolarization of resting membrane potential, and also reduction of input resistance, action potential duration, and spike firing. Moreover, ACOX1 inhibition increased rheobase current and afterhyperpolarization amplitude in granule cells. The results indicate, systemic inhibition of ACOX1 causes hypo-excitability of neuronal cells. These findings provide a new evidence on the involvement of peroxisome function and hepatic ACOX1 activity in brain fatty acid profile and the electrophysiological properties of dentate gyrus cells.

scholarly journals miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Eleonora Franzoni ◽  
Sam A Booker ◽  
Srinivas Parthasarathy ◽  
Frederick Rehfeld ◽  
Sabine Grosser ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Deleterious Effect ◽  
Adult Stem Cell ◽  
Cognitive Disorder ◽  
Neuronal Morphology ◽  
Intrinsic Excitability ◽  
Electrophysiological Properties ◽  
Physiological Properties ◽  
Stem Cell Niches ◽  
Cortical Lamination

miR-128, a brain-enriched microRNA, has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed. We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adult stem cell niches. Whereas premature miR-128 expression in progenitors for upper layer neurons leads to impaired neuronal migration and inappropriate branching, sponge-mediated inhibition results in overmigration. Within the upper layers, premature miR-128 expression reduces the complexity of dendritic arborization, associated with altered electrophysiological properties. We show that Phf6, a gene mutated in the cognitive disorder Börjeson-Forssman-Lehmann syndrome, is an important regulatory target for miR-128. Restoring PHF6 expression counteracts the deleterious effect of miR-128 on neuronal migration, outgrowth and intrinsic physiological properties. Our results place miR-128 upstream of PHF6 in a pathway vital for cortical lamination as well as for the development of neuronal morphology and intrinsic excitability.

scholarly journals Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jeffrey Lopez-Rojas ◽  
Martin Heine ◽  
Michael R. Kreutz
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Intrinsic Excitability
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