Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields

ABSTRACTNeuronal representations of spatial location and movement speed in the medial entorhinal cortex during the “active” theta state of the brain are important for memory-guided navigation and rely on visual inputs. However, little is known about how visual inputs change neural dynamics as a function of running speed and time. By manipulating visual inputs in mice, we demonstrate that changes in spatial stability of grid cell firing as a function of time correlate with changes in a proposed speed signal by local field potential theta frequency. In contrast, visual inputs do not affect the speed modulation of firing rates. Moreover, we provide evidence that sensory inputs other than visual inputs can support grid cell firing, though less accurately, in complete darkness. Finally, changes in spatial accuracy of grid cell firing on a 10-s time scale suggest that grid cell firing is a function of velocity signals integrated over past time.

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Effects of visual inputs on neural dynamics for coding of location and running speed in medial entorhinal cortex

eLife ◽

10.7554/elife.62500 ◽

2020 ◽

Vol 9 ◽

Author(s):

Holger Dannenberg ◽

Hallie Lazaro ◽

Pranav Nambiar ◽

Alec Hoyland ◽

Michael E Hasselmo

Keyword(s):

Entorhinal Cortex ◽

Field Potential ◽

Grid Cell ◽

Neuronal Firing ◽

Neural Dynamics ◽

Movement Speed ◽

Running Speed ◽

Medial Entorhinal Cortex ◽

Visual Inputs ◽

Cell Firing

Neuronal representations of spatial location and movement speed in the medial entorhinal cortex during the ‘active’ theta state of the brain are important for memory-guided navigation and rely on visual inputs. However, little is known about how visual inputs change neural dynamics as a function of running speed and time. By manipulating visual inputs in mice, we demonstrate that changes in spatial stability of grid cell firing correlate with changes in a proposed speed signal by local field potential theta frequency. In contrast, visual inputs do not alter the running speed-dependent gain in neuronal firing rates. Moreover, we provide evidence that sensory inputs other than visual inputs can support grid cell firing, though less accurately, in complete darkness. Finally, changes in spatial accuracy of grid cell firing on a 10 s time scale suggest that grid cell firing is a function of velocity signals integrated over past time.

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Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa022 ◽

2020 ◽

Vol 23 (7) ◽

pp. 459-468 ◽

Cited By ~ 2

Author(s):

Xuejiao Wang ◽

Yingzhuo Li ◽

Jingyu Chen ◽

Zijie Li ◽

Jinhong Li ◽

...

Keyword(s):

Prefrontal Cortex ◽

Steady State ◽

Local Field ◽

Local Field Potential ◽

Phase Locking ◽

Field Potential ◽

Medial Geniculate Body ◽

Systemic Administration ◽

Mk 801 ◽

Medial Geniculate

Abstract Background Systemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus. Methods We implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB). Results We found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801. Conclusion Our data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.

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Author response for "Activation of cannabinoid type 1 receptors decreases the synchronization of local field potential oscillations in the hippocampus and entorhinal cortex and prolongs the interresponse time during a differential‐reinforcement‐of‐low‐rate (DRL) task"

10.1111/ejn.14856/v2/response1 ◽

2020 ◽

Author(s):

Wan‐Ting Liao ◽

Chao‐Lin Chang ◽

Yi‐Tse Hsiao

Keyword(s):

Entorhinal Cortex ◽

Local Field ◽

Local Field Potential ◽

Differential Reinforcement ◽

Interresponse Time ◽

Field Potential ◽

Author Response ◽

Potential Oscillations ◽

Low Rate

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Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0523 ◽

2014 ◽

Vol 369 (1635) ◽

pp. 20120523 ◽

Cited By ~ 28

Author(s):

Michael E. Hasselmo

Keyword(s):

Resonance Frequency ◽

Entorhinal Cortex ◽

Functional Role ◽

Grid Cell ◽

Medial Septum ◽

Medial Entorhinal Cortex ◽

Spatial Periodicity ◽

Cell Firing ◽

Rebound Spiking ◽

Relationship Of

Data show a relationship of cellular resonance and network oscillations in the entorhinal cortex to the spatial periodicity of grid cells. This paper presents a model that simulates the resonance and rebound spiking properties of entorhinal neurons to generate spatial periodicity dependent upon phasic input from medial septum. The model shows that a difference in spatial periodicity can result from a difference in neuronal resonance frequency that replicates data from several experiments. The model also demonstrates a functional role for the phenomenon of theta cycle skipping in the medial entorhinal cortex.

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How to build a grid cell

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0520 ◽

2014 ◽

Vol 369 (1635) ◽

pp. 20120520 ◽

Cited By ~ 8

Author(s):

Christoph Schmidt-Hieber ◽

Michael Häusser

Keyword(s):

Entorhinal Cortex ◽

Action Potentials ◽

Path Integration ◽

Grid Cell ◽

Medial Entorhinal Cortex ◽

Synaptic Inputs ◽

New Findings ◽

Cell Firing

Neurons in the medial entorhinal cortex fire action potentials at regular spatial intervals, creating a striking grid-like pattern of spike rates spanning the whole environment of a navigating animal. This remarkable spatial code may represent a neural map for path integration. Recent advances using patch-clamp recordings from entorhinal cortex neurons in vitro and in vivo have revealed how the microcircuitry in the medial entorhinal cortex may contribute to grid cell firing patterns, and how grid cells may transform synaptic inputs into spike output during firing field crossings. These new findings provide key insights into the ingredients necessary to build a grid cell.

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Theta-frequency resonance as the scale of input-output mapping in the medial entorhinal cortex

10.1101/369025 ◽

2018 ◽

Author(s):

Nupur Katyare ◽

Sujit Sikdar

Keyword(s):

Firing Rate ◽

Entorhinal Cortex ◽

Grid Cell ◽

Synaptic Activity ◽

Spatial Period ◽

Hcn Channels ◽

Medial Entorhinal Cortex ◽

Frequency Resonance ◽

Theta Frequency

Grid cell spatial period is thought to be dictated by a mapping between the speed-direction modulated excitatory inputs, and consequent modulation of the firing rate, yet, the exact underlying mechanisms are not known. Here, through experiments on the medial entorhinal cortex stellate cells, subjected to in-vivo like stochastic synaptic activity through the dynamic clamp, we show that such mapping can emerge from a theta-frequency resonance in the signal gain, which is HCN sensitive, robust to noise, and is potent enough to modulate the synaptic responses in the theta frequency. This modulation also extends to the corresponding theta-gamma modulation of the firing rate, the slope of whose excitation mediated increase is steeper in the presence of HCN channels. We also show that in the cells devoid of HCN channels, inhibition can emulate their role. Considering the dorso-ventral gradients of HCN and inhibition, which are present aligned to the grid spacing gradient in the medial entorhinal cortex, these findings should be noteworthy.

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