<i>In vitro</i> characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

Walsh, Darren; Brown, Jon T.; Randall, Andrew D.

doi:10.1113/jp273915

Cited by 16 publications

(31 citation statements)

References 66 publications

(174 reference statements)

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“…Interestingly, this did not correspond to a significant decrease in the number of neurons exhibiting 120 spontaneous AP generation in the absence of applied stimuli ( Fig 1B, (Walsh et al, 2017) and found, predictably, that Vm varies between these populations. As 124 such, the increased proportion of hyperpolarised neurons in J20 mice could be a manifestation of an 125 increase in the relative proportion of active neurons displaying low firing frequencies associated with 126 hyperpolarised Vm.…”

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confidence: 85%

“…95% O2 82 /5% CO2). A single coronal section containing the rostral Re was identified as described previously 83 (Walsh et al, 2017). 84…”

Section: Animals and Tissue Preparation 72mentioning

confidence: 99%

“…A series of voltage 223 steps was applied, ranging from -68 to -40 mV, from a holding potential of -78 mV (see Figure 5D). In 224 response to sufficiently large voltage steps an additional inward current was observed which was 225 evidently larger and displayed longer activation and inactivation kinetics than the inactivating T-type 226 channel currents (Walsh et al, 2017). These likely arise from the initial activation of a large HVA Ca 2+ 227 channel current component.…”

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confidence: 98%

“…Previous recordings made within our lab from young adult (16-18 weeks) male mice indicate that Re 109 neurons typically display a relatively depolarised resting membrane potential (Vm) and an associated 110 propensity to fire spontaneous action potentials (APs) in the absence of any external depolarising 111 input (Walsh et al, 2017). To assess whether the spontaneous firing behaviours of Re neurons differed 112 between WT and TG mice, Vm was recorded, in the absence of exogenous stimuli, for 60 s following 113 breaking in to the whole cell mode.…”

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confidence: 99%

“…We 202 wished to assess whether the increased propensity to rebound fire in TG mice may result from of 203 alterations to the amplitude or kinetics of T-type calcium channels. One would expect that such a 204 change would manifest as an alteration in the number of neurons exhibiting sub-threshold and supra-205 threshold afterdeoplarisations (ADP), a feature underpinned in Re neurons by T-type calcium 206 conductances (Walsh et al, 2017). In order to quantify ADP amplitude a single spike was elicited with 207 a large (2 nA), short (1.3 ms) depolarising current injection applied at a set prestimulus potential of -208 80 mV.…”

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confidence: 99%

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Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer’s disease

Walsh

Brown

Randall

2019

Preprint

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Key Points Alterations in the neurophysiology of hippocampal and cortical neurons has been linked to network hyperexcitability in mouse models of amyloidopathy.  The nucleus reuniens (Re) is part of a cognitive network involving the hippocampal formation and prefrontal cortex. Increased cellular activity in Re has been linked to the generation of hippocampal-thalamo-cortical seizure activity in J20 mice.  Re neurons display hyperpolarised resting membrane potentials in J20 mice. Passive membrane properties are unaffected by transgene expression. Re neurons recorded from J20 mice did not exhibit increased excitability in response to depolarising current stimuli but did exhibit an increased propensity to rebound burst following hyperpolarising current stimuli. This increased rebound firing was not a result of changes in T-type Ca 2+ conductances. Finally we observed a decrease in AP width.  These results help us understand how altered Re cellular neurophysiology may contribute to hippocampal-thalamo-cortical hyperexcitability in J20 mice. Abstract 1Transgenic mice that overproduce beta-amyloid (Aβ) peptides exhibit neurophysiological alterations 2 at the cellular, synaptic and network levels. Recently, increased neuronal activity in nucleus reuniens 3 (Re), has been linked to hyperexcitability within hippocampal-thalamo-cortical networks in the J20 4 mouse model of amyloidopathy. Here in vitro whole-cell patch clamp recordings were used to 5 compare old pathology-bearing J20 mice and wild-type controls to examine whether alterations to the 6 intrinsic electrophysiological properties of Re neurons could contribute to the amyloidopathy-7 associated Re hyperactivity. A greater proportion of Re neurons displayed a hyperpolarised membrane 8 potential in J20 mice without changes to the incidence or frequency of spontaneous action potential 9 (AP) generation. Passive membrane properties were independent of transgene expression. Re 10 neurons recorded from J20 mice did not exhibit increased AP generation in response to depolarising 11 current stimuli but did exhibit an increased propensity to rebound burst following hyperpolarising 12 current stimuli. This increase in rebound firing does not appear to result from alterations to T-type 13 calcium channels. Finally, in J20 mice there was an ~8% reduction in spike width, similar to what we 14 and others have reported in CA1 pyramidal neurons from multiple amyloidopathy mice. We conclude 15 that alterations to the intrinsic properties of Re neurons may contribute to the hyperexcitability 16 observed in hippocampal-thalmo-cortical circuits under pathological Aβ load. 17

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confidence: 85%

“…95% O2 82 /5% CO2). A single coronal section containing the rostral Re was identified as described previously 83 (Walsh et al, 2017). 84…”

Section: Animals and Tissue Preparation 72mentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer’s disease

Walsh

Brown

Randall

2019

Preprint

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Calretinin and calbindin architecture of the midline thalamus associated with prefrontal–hippocampal circuitry

et al. 2020

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The midline thalamus bi-directionally connects the medial prefrontal cortex (mPFC) and hippocampus (HC) creating a unique cortico-thalamo-cortico circuit fundamental to memory and executive function.While the anatomical connectivity of midline thalamus has been thoroughly investigated, little is known about its cellular organization within each nucleus. Here we used immunohistological techniques to examine cellular distributions in the midline thalamus based on the calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). We also examined these calcium binding proteins in a population of reuniens cells known to project to both mPFC and HC using a dual fluorescence retrograde adenoassociated virus (AAV) based tracing approach. These dual reuniens mPFC-HC projecting cells, in particular, are thought to be important for synchronizing mPFC and HC activity. First, we confirmed the absence of PV + neurons in the midline thalamus. Second, we found a common pattern of CR + and CB + cells throughout midline thalamus with CR + cells running along the nearby third ventricle (3V) and penetrating the midline. CB + cells were consistently more lateral and toward the middle of the dorsalventral extent of the midline thalamus. Notably, single-labeled CR + and CB + zones were partially overlapping and included dual-labeled CR + /CB + cells. Within RE, we also observed a CR and CB subzone specific diversity. Interestingly, dual mPFC-HC projecting neurons in RE expressed none of the calcium binding proteins examined, but were contained in nests of CR + and CB + cells. Overall, the midline thalamus was well organized into CR + and CB + rich zones distributed throughout the region, with dual mPFC-HC projecting cells in reuniens representing a unique cell population. These results provide a cytoarchitectural organization in the midline thalamus based on calcium binding protein expression, and sets the stage for future cell-type specific interrogations of the functional role of these different cell populations in mPFC-HC interactions..

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The Mouse Thalamus

Schröder

Moser

Huggenberger

2020

Neuroanatomy of the Mouse

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In vitro characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

Cited by 16 publications

References 66 publications

Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer’s disease

Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer’s disease

Calretinin and calbindin architecture of the midline thalamus associated with prefrontal–hippocampal circuitry

The Mouse Thalamus

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