Entorhinal cortex directs learning-related changes in CA1 representations

Mapping Intimacies ◽

10.1101/2021.12.10.472158 ◽

2021 ◽

Author(s):

Christine Grienberger ◽

Jeffrey C Magee

Keyword(s):

Synaptic Plasticity ◽

Entorhinal Cortex ◽

Activity Pattern ◽

Brain Activity ◽

Adaptive Behaviors ◽

Place Field ◽

Population Activity ◽

Field Density ◽

Hippocampal Ca1

Learning-related changes in brain activity are thought to underlie adaptive behaviors. For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus. However, how this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioral timescale synaptic plasticity (BTSP). BTSP is known to be driven by dendritic voltage signals that we hypothesized were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that appears to be specifically adapted to the behaviorally relevant features of the environment.

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Bidirectional synaptic plasticity rapidly modifies hippocampal representations

eLife ◽

10.7554/elife.73046 ◽

2021 ◽

Vol 10 ◽

Author(s):

Aaron D Milstein ◽

Yiding Li ◽

Katie C Bittner ◽

Christine Grienberger ◽

Ivan Soltesz ◽

...

Keyword(s):

Synaptic Plasticity ◽

Synaptic Weight ◽

Standard Form ◽

Learning Rule ◽

Weight Changes ◽

Place Field ◽

Plateau Potentials ◽

Population Activity ◽

Neural Adaptations ◽

Place Fields

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience.

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Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Nutrients ◽

10.3390/nu10060749 ◽

2018 ◽

Vol 10 (6) ◽

pp. 749 ◽

Cited By ~ 1

Author(s):

Stine Hansen ◽

Jane Jørgensen ◽

Jens Nyengaard ◽

Jens Lykkesfeldt ◽

Pernille Tveden-Nyborg

Keyword(s):

Synaptic Plasticity ◽

Vitamin C ◽

Guinea Pig ◽

Early Life ◽

Pyramidal Neurons ◽

Pig Model ◽

Vitamin C Deficiency ◽

Ca1 Pyramidal Neurons ◽

Hippocampal Ca1 ◽

Guinea Pig Model

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Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.1997.77.6.3013 ◽

1997 ◽

Vol 77 (6) ◽

pp. 3013-3020 ◽

Cited By ~ 154

Author(s):

Hiroshi Katsuki ◽

Yukitoshi Izumi ◽

Charles F. Zorumski

Keyword(s):

Synaptic Plasticity ◽

Receptor Antagonist ◽

Hippocampal Slices ◽

Stimulus Frequency ◽

Long Term Potentiation ◽

Receptor Activation ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Hippocampal Ca1

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

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Brain activity pattern changes after adaptive working memory training in multiple sclerosis

Brain Imaging and Behavior ◽

10.1007/s11682-018-9984-z ◽

2018 ◽

Vol 14 (1) ◽

pp. 142-154 ◽

Cited By ~ 8

Author(s):

Laura Bonzano ◽

Ludovico Pedullà ◽

Matteo Pardini ◽

Andrea Tacchino ◽

Paola Zaratin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Working Memory ◽

Activity Pattern ◽

Brain Activity ◽

Working Memory Training ◽

Memory Training ◽

Brain Activity Pattern

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Muscarinic Induction of Synchronous Population Activity in the Entorhinal Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.17-17-06729.1997 ◽

1997 ◽

Vol 17 (17) ◽

pp. 6729-6744 ◽

Cited By ~ 97

Author(s):

Clayton T. Dickson ◽

Angel Alonso

Keyword(s):

Entorhinal Cortex ◽

Population Activity

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Orientation and color tuning of the human visual gamma rhythm

10.1101/2021.04.23.441193 ◽

2021 ◽

Author(s):

Ye Li ◽

William Bosking ◽

Michael S Beauchamp ◽

Sameer A Sheth ◽

Daniel Yoshor ◽

...

Keyword(s):

Visual Cortex ◽

Large Scale ◽

Brain Activity ◽

Population Level ◽

Gamma Oscillations ◽

Cell Orientation ◽

Population Activity ◽

Color Tuning ◽

Human Visual Cortex ◽

Gamma Rhythm

Narrowband gamma oscillations (NBG: ~20-60Hz) in visual cortex reflect rhythmic fluctuations in population activity generated by underlying circuits tuned for stimulus location, orientation, and color. Consequently, the amplitude and frequency of induced NBG activity is highly sensitive to these stimulus features. For example, in the non-human primate, NBG displays biases in orientation and color tuning at the population level. Such biases may relate to recent reports describing the large-scale organization of single-cell orientation and color tuning in visual cortex, thus providing a potential bridge between measurements made at different scales. Similar biases in NBG population tuning have been predicted to exist in the human visual cortex, but this has yet to be fully examined. Using intracranial recordings from human visual cortex, we investigated the tuning of NBG to orientation and color, both independently and in conjunction. NBG was shown to display a cardinal orientation bias (horizontal) and also an end- and mid-spectral color bias (red/blue and green). When jointly probed, the cardinal bias for orientation was attenuated and an end-spectral preference for red and blue predominated. These data both elaborate on the close, yet complex, link between the population dynamics driving NBG oscillations and known feature selectivity biases in visual cortex, adding to a growing set of stimulus dependencies associated with the genesis of NBG. Together, these two factors may provide a fruitful testing ground for examining multi-scale models of brain activity, and impose new constraints on the functional significance of the visual gamma rhythm.

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Sub-second dynamics of theta-gamma coupling in hippocampal CA1

eLife ◽

10.7554/elife.44320 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 3

Author(s):

Lu Zhang ◽

John Lee ◽

Christopher Rozell ◽

Annabelle C Singer

Keyword(s):

Neural Coding ◽

Brain Activity ◽

Gamma Oscillations ◽

New Approach ◽

Excitatory State ◽

Hippocampal Ca1 ◽

Frequent Switching ◽

Brain States ◽

Oscillatory Brain Activity ◽

Oscillatory Coupling

Oscillatory brain activity reflects different internal brain states including neurons’ excitatory state and synchrony among neurons. However, characterizing these states is complicated by the fact that different oscillations are often coupled, such as gamma oscillations nested in theta in the hippocampus, and changes in coupling are thought to reflect distinct states. Here, we describe a new method to separate single oscillatory cycles into distinct states based on frequency and phase coupling. Using this method, we identified four theta-gamma coupling states in rat hippocampal CA1. These states differed in abundance across behaviors, phase synchrony with other hippocampal subregions, and neural coding properties suggesting that these states are functionally distinct. We captured cycle-to-cycle changes in oscillatory coupling states and found frequent switching between theta-gamma states showing that the hippocampus rapidly shifts between different functional states. This method provides a new approach to investigate oscillatory brain dynamics broadly.

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Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020810118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2020810118

Author(s):

Ye Wang ◽

Wing-Yu Fu ◽

Kit Cheung ◽

Kwok-Wang Hung ◽

Congping Chen ◽

...

Keyword(s):

Synaptic Plasticity ◽

Neuronal Activity ◽

Hippocampal Slices ◽

Memory Formation ◽

Conditional Knockout ◽

Acute Administration ◽

Excitatory Synapses ◽

Homeostatic Synaptic Plasticity ◽

Hippocampal Ca1

Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.

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