scholarly journals Structural Spine Plasticity in Olfaction: Memory and Forgetting, Enhanced vs. Reduced Discriminability after Learning

2020 ◽  
Author(s):  
John Hongyu Meng ◽  
Hermann Riecke
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cell ◽  
Granule Cells ◽  
Cell Activity ◽  
Mitral Cell ◽  
Pattern Separation ◽  
Type Model ◽  
Sensory Stimuli ◽  
Reciprocal Connections ◽  
Spine Plasticity

AbstractHow animals learn to discriminate between different sensory stimuli is an intriguing question. An important, common step towards discrimination is the enhancement of differences between the representations of relevant stimuli. This can be part of the learning process. In rodents, the olfac-tory bulb, which is known to contribute to this pattern separation, exhibits extensive structural synaptic plasticity even in adult animals: reciprocal connections between excitatory mitral cells and inhibitory granule cells are persistently formed and eliminated, correlated with mitral cell and granule cell activity. Here we present a Hebbian-type model for this plasticity. It captures the experimental observation that the same learning protocol that enhanced the discriminability of similar stimuli actually reduced that of dissimilar stimuli. The model predicts that the learned bulbar network structure is remembered across training with additional stimuli, unless the new stimuli interfere with the representations of previously learned ones.

scholarly journals Efficient generation of reciprocal signals by inhibition

2012 ◽  
Vol 107 (9) ◽  
pp. 2453-2462 ◽  
Author(s):  
Sung-min Park ◽  
Esra Tara ◽  
Kamran Khodakhah
Keyword(s):  
Purkinje Cells ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Common Mechanism ◽  
Input Output ◽  
Firing Rates ◽  
Neuronal Computation ◽  
The Brain

Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a second set of principal neurons. This circuitry can be the substrate for generation of reciprocal signals. Here we demonstrate that this equivalent circuit in the cerebellar cortex enables the reciprocal firing rates of Purkinje cells to be efficiently generated from a common set of mossy fiber inputs. The activity of a mossy fiber is relayed to Purkinje cells positioned immediately above it by excitatory granule cells. The firing rates of these Purkinje cells increase as a linear function of mossy fiber, and thus granule cell, activity. In addition to exciting Purkinje cells positioned immediately above it, the activity of a mossy fiber is relayed to laterally positioned Purkinje cells by a disynaptic granule cell → molecular layer interneuron pathway. Here we show in acutely prepared cerebellar slices that the input-output relationship of these laterally positioned Purkinje cells is linear and reciprocal to the first set. A similar linear input-output relationship between decreases in Purkinje cell firing and strength of stimulation of laterally positioned granule cells was also observed in vivo. Use of interneurons to generate reciprocal firing rates may be a common mechanism by which the brain generates reciprocal signals.

scholarly journals Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Heterosynaptic Plasticity ◽  
Spine Plasticity

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.

scholarly journals Normalization of input patterns in an associative network

2014 ◽  
Vol 111 (3) ◽  
pp. 544-551 ◽  
Author(s):  
Andreas Liu ◽  
Wade G. Regehr
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Cell Activity ◽  
Learning Rule ◽  
Brain Structures ◽  
Total Activity ◽  
Principal Cell ◽  
Functional Interpretation ◽  
Wide Range ◽  
Perceptron Learning

Numerous brain structures have a cerebellum-like architecture in which inputs diverge onto a large number of granule cells that converge onto principal cells. Plasticity at granule cell-to-principal cell synapses is thought to allow these structures to associate spatially distributed patterns of granule cell activity with appropriate principal cell responses. Storing large sets of associations requires the patterns involved to be normalized, i.e., to have similar total amounts of granule cell activity. Using a general model of associative learning, we describe two ways in which granule cells can be configured to promote normalization. First, we show how heterogeneity in firing thresholds across granule cells can restrict pattern-to-pattern variation in total activity while also limiting spatial overlap between patterns. These effects combine to allow fast and flexible learning. Second, we show that the perceptron learning rule selectively silences those synapses that contribute most to pattern-to-pattern variation in the total input to a principal cell. This provides a simple functional interpretation for the experimental observation that many granule cell-to-Purkinje cell synapses in the cerebellum are silent. Since our model is quite general, these principles may apply to a wide range of associative circuits.

scholarly journals Olfactory bulb granule cells: specialized to link coactive glomerular columns for percept generation and discrimination of odors

2021 ◽  
Author(s):  
Veronica Egger ◽  
Thomas Kuner
Keyword(s):  
Granule Cell ◽  
Lateral Inhibition ◽  
Granule Cells ◽  
Cell Activity ◽  
Sensory System ◽  
Gaba Release ◽  
Odor Discrimination ◽  
Synaptic Proteins ◽  
Cooperative Action ◽  
Odor Processing

AbstractThe role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the purpose of reciprocal spines and the mechanisms for GABA release, the apparently low firing activity and recurrent inhibitory drive of granule cells, the missing proof for functional reciprocal connectivity, and the apparently negligible contribution to lateral inhibition. Here, we summarize recent results with regard to both the mechanisms of GABA release and the behavioral relevance of granule cell activity during odor discrimination. We outline a novel hypothesis that has the potential to resolve most of these enigmas and allows further predictions on the function of granule cells in odor processing. Briefly, recent findings imply that GABA release from the reciprocal spine requires a local spine action potential and the cooperative action of NMDA receptors and high voltage-activated Ca2+ channels. Thus, lateral inhibition is conditional on activity in the principal neurons connected to a granule cell and tightly intertwined with recurrent inhibition. This notion allows us to infer that lateral inhibition between principal neurons occurs “on demand,” i.e., selectively on coactive mitral and tufted cells, and thus can provide directed, dynamically switched lateral inhibition in a sensory system with 1000 input channels organized in glomerular columns. The mechanistic underpinnings of this hypothesis concur with findings from odor discrimination behavior in mice with synaptic proteins deleted in granule cells. In summary, our hypothesis explains the unusual microcircuit of the granule cell reciprocal spine as a means of olfactory combinatorial coding.

scholarly journals Serotonin regulates dynamics of cerebellar granule cell activity by modulating tonic inhibition

2019 ◽  
Vol 121 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Elizabeth Fleming ◽  
Court Hull
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Spike Timing ◽  
Tonic Inhibition ◽  
Granule Cell Layer ◽  
Golgi Cells ◽  
Cell Depolarization ◽  
Feed Forward Inhibition

Understanding how afferent information is integrated by cortical structures requires identifying the factors shaping excitation and inhibition within their input layers. The input layer of the cerebellar cortex integrates diverse sensorimotor information to enable learned associations that refine the dynamics of movement. Specifically, mossy fiber afferents relay sensorimotor input into the cerebellum to excite granule cells, whose activity is regulated by inhibitory Golgi cells. To test how this integration can be modulated, we have used an acute brain slice preparation from young adult rats and found that encoding of mossy fiber input in the cerebellar granule cell layer can be regulated by serotonin (5-hydroxytryptamine, 5-HT) via a specific action on Golgi cells. We find that 5-HT depolarizes Golgi cells, likely by activating 5-HT2A receptors, but does not directly act on either granule cells or mossy fibers. As a result of Golgi cell depolarization, 5-HT significantly increases tonic inhibition onto both granule cells and Golgi cells. 5-HT-mediated Golgi cell depolarization is not sufficient, however, to alter the probability or timing of mossy fiber-evoked feed-forward inhibition onto granule cells. Together, increased granule cell tonic inhibition paired with normal feed-forward inhibition acts to reduce granule cell spike probability without altering spike timing. Hence, these data provide a circuit mechanism by which 5-HT can reduce granule cell activity without altering temporal representations of mossy fiber input. Such changes in network integration could enable flexible, state-specific suppression of cerebellar sensorimotor input that should not be learned or enable reversal learning for unwanted associations. NEW & NOTEWORTHY Serotonin (5-hydroxytryptamine, 5-HT) regulates synaptic integration at the input stage of cerebellar processing by increasing tonic inhibition of granule cells. This circuit mechanism reduces the probability of granule cell spiking without altering spike timing, thus suppressing cerebellar input without altering its temporal representation in the granule cell layer.

Intracellular responses of identified rat olfactory bulb interneurons to electrical and odor stimulation

1990 ◽  
Vol 64 (3) ◽  
pp. 932-947 ◽  
Author(s):  
D. P. Wellis ◽  
J. W. Scott
Keyword(s):  
Electrical Stimulation ◽  
Olfactory Bulb ◽  
Granule Cell ◽  
Action Potentials ◽  
Granule Cells ◽  
Olfactory Nerve ◽  
Mitral Cell ◽  
Intracellular Recordings ◽  
Postsynaptic Potential ◽  
Stimulation Of

1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20-30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of Effect of Mossy Fiber-Released Zinc on Granule Cell GABAAReceptors in the Pilocarpine Model of Epilepsy

2001 ◽  
Vol 85 (5) ◽  
pp. 1932-1940 ◽  
Author(s):  
Péter Molnár ◽  
J. Victor Nadler
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Cell Activity ◽  
Mean Amplitude ◽  
Proximal Portion ◽  
Receptor Function ◽  
Mossy Fiber Pathway

The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in the epileptic brain and serves as a mechanism for synchronization of granule cell epileptiform activity. It has been suggested that this pathway also promotes epileptiform activity by inhibiting GABAAreceptor function through release of zinc. Hippocampal slices from pilocarpine-treated rats were used to evaluate this hypothesis. The rats had developed status epilepticus after pilocarpine administration, followed by robust recurrent mossy fiber growth. The ability of exogenously applied zinc to depress GABAAreceptor function in dentate granule cells depended on removal of polyvalent anions from the superfusion medium. Under these conditions, 200 μM zinc reduced the amplitude of the current evoked by applying muscimol to the proximal portion of the granule cell dendrite (23%). It also reduced the mean amplitude (31%) and frequency (36%) of miniature inhibitory postsynaptic currents. Nevertheless, repetitive mossy fiber stimulation (10 Hz for 1 s, 100 Hz for 1 s, or 10 Hz for 5 min) at maximal intensity did not affect GABAAreceptor-mediated currents evoked by photorelease of GABA onto the proximal portion of the dendrite, where recurrent mossy fiber synapses were located. These results could not be explained by stimulation-induced depletion of zinc from the recurrent mossy fiber boutons. Negative results were obtained even during exposure to conditions that promoted transmitter release and synchronized granule cell activity (6 mM [K+]o, nominally Mg2+-free medium, 33°C). These results suggest that zinc released from the recurrent mossy fiber pathway did not reach a concentration at postsynaptic GABAAreceptors sufficient to inhibit agonist-evoked activation.

scholarly journals An emergent temporal basis set robustly supports cerebellar time-series learning

2022 ◽  
Author(s):  
Jesse I Gilmer ◽  
Michael A Farries ◽  
Zachary P Kilpatrick ◽  
Ioannis Delis ◽  
Abigail L Person
Keyword(s):  
Time Series ◽  
Granule Cell ◽  
Cell Activity ◽  
Pattern Separation ◽  
Basis Set ◽  
Granule Cell Layer ◽  
Series Data ◽  
Time Interval ◽  
Classification Tasks ◽  
Temporal Basis

Learning plays a key role in the function of many neural circuits. The cerebellum is considered a learning machine essential for time interval estimation underlying motor coordination and other behaviors. Theoretical work has proposed that the cerebellar input recipient structure, the granule cell layer (GCL), performs pattern separation of inputs that facilitates learning in Purkinje cells (P-cells). However, the relationship between input reformatting and learning outcomes has remained debated, with roles emphasized for pattern separation features from sparsification to decorrelation. We took a novel approach by training a minimalist model of the cerebellar cortex to learn complex time-series data from naturalistic inputs, in contrast to traditional classification tasks. The model robustly produced temporal basis sets from naturalistic inputs, and the resultant GCL output supported learning of temporally complex target functions. Learning favored surprisingly dense granule cell activity, yet the key statistical features in GCL population activity that drove learning differed from those seen previously for classification tasks. Moreover, different cerebellar tasks were supported by diverse pattern separation features that matched the demands of the tasks. These findings advance testable hypotheses for mechanisms of temporal basis set formation and predict that population statistics of granule cell activity may differ across cerebellar regions to support distinct behaviors.

scholarly journals Synaptic Plasticity and Excitation-Inhibition Balance in the Dentate Gyrus: Insights fromIn VivoRecordings in Neuroligin-1, Neuroligin-2, and Collybistin Knockouts

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Peter Jedlicka ◽  
Julia Muellerleile ◽  
Stephan W. Schwarzacher
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Molecular Mechanisms ◽  
Granule Cells ◽  
Functional Characterization ◽  
Inhibitory Synapses ◽  
Spatial Learning And Memory ◽  
Dentate Granule Cell

The hippocampal dentate gyrus plays a role in spatial learning and memory and is thought to encode differences between similar environments. The integrity of excitatory and inhibitory transmission and a fine balance between them is essential for efficient processing of information. Therefore, identification and functional characterization of crucial molecular players at excitatory and inhibitory inputs is critical for understanding the dentate gyrus function. In this minireview, we discuss recent studies unraveling molecular mechanisms of excitatory/inhibitory synaptic transmission, long-term synaptic plasticity, and dentate granule cell excitability in the hippocampus of live animals. We focus on the role of three major postsynaptic proteins localized at excitatory (neuroligin-1) and inhibitory synapses (neuroligin-2 and collybistin).In vivorecordings of field potentials have the advantage of characterizing the effects of the loss of these proteins on the input-output function of granule cells embedded in a network with intact connectivity. The lack of neuroligin-1 leads to deficient synaptic plasticity and reduced excitation but normal granule cell output, suggesting unaltered excitation-inhibition ratio. In contrast, the lack of neuroligin-2 and collybistin reduces inhibition resulting in a shift towards excitation of the dentate circuitry.

scholarly journals Circuit-based interventions in the dentate gyrus rescue epilepsy-associated cognitive dysfunction

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2705-2721 ◽  
Author(s):  
Julia B Kahn ◽  
Russell G Port ◽  
Cuiyong Yue ◽  
Hajime Takano ◽  
Douglas A Coulter
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Cognitive Dysfunction ◽  
Temporal Lobe ◽  
Granule Cell ◽  
Granule Cells ◽  
Dorsal Hippocampus ◽  
Cell Activity ◽  
Downstream Target ◽  
Behavioural Performance

Abstract Temporal lobe epilepsy is associated with significant structural pathology in the hippocampus. In the dentate gyrus, the summative effect of these pathologies is massive hyperexcitability in the granule cells, generating both increased seizure susceptibility and cognitive deficits. To date, therapeutic approaches have failed to improve the cognitive symptoms in fully developed, chronic epilepsy. As the dentate’s principal signalling population, the granule cells’ aggregate excitability has the potential to provide a mechanistically-independent downstream target. We examined whether normalizing epilepsy-associated granule cell hyperexcitability—without correcting the underlying structural circuit disruptions—would constitute an effective therapeutic approach for cognitive dysfunction. In the systemic pilocarpine mouse model of temporal lobe epilepsy, the epileptic dentate gyrus excessively recruits granule cells in behavioural contexts, not just during seizure events, and these mice fail to perform on a dentate-mediated spatial discrimination task. Acutely reducing dorsal granule cell hyperactivity in chronically epileptic mice via either of two distinct inhibitory chemogenetic receptors rescued behavioural performance such that they responded comparably to wild type mice. Furthermore, recreating granule cell hyperexcitability in control mice via excitatory chemogenetic receptors, without altering normal circuit anatomy, recapitulated spatial memory deficits observed in epileptic mice. However, making the granule cells overly quiescent in both epileptic and control mice again disrupted behavioural performance. These bidirectional manipulations reveal that there is a permissive excitability window for granule cells that is necessary to support successful behavioural performance. Chemogenetic effects were specific to the targeted dorsal hippocampus, as hippocampal-independent and ventral hippocampal-dependent behaviours remained unaffected. Fos expression demonstrated that chemogenetics can modulate granule cell recruitment via behaviourally relevant inputs. Rather than driving cell activity deterministically or spontaneously, chemogenetic intervention merely modulates the behaviourally permissive activity window in which the circuit operates. We conclude that restoring appropriate principal cell tuning via circuit-based therapies, irrespective of the mechanisms generating the disease-related hyperactivity, is a promising translational approach.

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