Cracks in the foundation: The experience of care aides in long-term care homes during the COVID-19 pandemic.

BACKGROUND: Care aides (certified nursing assistants, personal support workers) are the largest workforce in long-term care (LTC) homes (nursing homes). They provide as much as 90% of direct care to residents. Their health and well-being directly affect both quality of care and quality of life for residents. The aim of this study was to understand the impact of COVID-19 on care aides working in LTC homes during the first year of the pandemic. METHODS: We conducted semi-structured interviews with a convenience sample of 52 care aides from 8 LTC homes in Alberta and one in British Columbia, Canada, between January and April 2021. Nursing homes were purposively selected across: (1) ownership model and (2) COVID impact (the rate of COVID infections reported from March to December 2020). Interviews were recorded and analyzed using inductive content analysis. RESULTS: Care aides were mainly female (94%) and older (74% aged 40 years or older). Most spoke English as an additional language (76%), 54% worked full-time in LTC homes, and 37% worked multiple positions before "one worksite policies" were implemented. Two themes emerged from our analysis: (1) Care aides experienced mental and emotional distress from enforcing resident isolation, grief related to resident deaths, fear of contracting and spreading COVID-19, increased workload combined with staffing shortages, and rapidly changing policies. (2) Care aides' resilience was supported by their strong relationships, faith and community, and capacity to maintain positive attitudes. CONCLUSIONS: These findings suggest significant, ongoing adverse effects for care aides in LTC homes from working through the COVID-19 pandemic. Our data demonstrate the considerable strength of this occupational group. Our results emphasize the urgent need to appropriately and meaningfully support care aides' mental health and well-being and adequately resource this workforce. We recommend improved policy guidelines and interventions.

Sensory Over-responsivity and Aberrant Plasticity in Cerebellar Cortex in a Mouse Model of Syndromic Autism.

Background: Patients with autism spectrum disorder often show altered responses to sensory stimuli as well as motor deficits, including an impairment of delay eyeblink conditioning, which involves integration of sensory signals in the cerebellum. Here, we identify abnormalities in parallel fiber (PF) and climbing fiber (CF) signaling in the mouse cerebellar cortex that may contribute to these pathologies. Methods: We used a mouse model for the human 15q11-13 duplication (patDp/+) and studied responses to sensory stimuli in Purkinje cells from awake mice using two-photon imaging of GCaMP6f signals. Moreover, we examined synaptic transmission and plasticity using in vitro electrophysiological, immunohistochemical, and confocal microscopic techniques. Results: We found that spontaneous and sensory-evoked CF-calcium transients are enhanced in patDp/+ Purkinje cells, and aversive movements are more severe across sensory modalities. We observed increased expression of the synaptic organizer NRXN1 at CF synapses and ectopic spread of these synapses to fine dendrites. CF-excitatory postsynaptic currents recorded from Purkinje cells are enlarged in patDp/+ mice, while responses to PF stimulation are reduced. Confocal measurements show reduced PF+CF-evoked spine calcium transients, a key trigger for PF long-term depression, one of several plasticity types required for eyeblink conditioning learning. Long-term depression is impaired in patDp/+ mice but is rescued on pharmacological enhancement of calcium signaling. Conclusions: Our findings suggest that this genetic abnormality causes a pathological inflation of CF signaling, possibly resulting from enhanced NRXN1 expression, with consequences for the representation of sensory stimuli by the CF input and for PF synaptic organization and plasticity.

Care aides' perceptions of caring for residents with a history of psychological trauma in Western Canadian care homes.

OBJECTIVE: To explore care aide perceptions of caring for residents who aides perceived had past psychological trauma. METHODS: Through cognitive interviews, we developed a definition of trauma for four survey questions about caring for residents with psychological trauma. We added these questions to our routine care aide survey in 91 care homes in Western Canada (September 2019 to February 2020). We asked if care aides perceived that they were caring for residents with trauma, how often, types of trauma experienced, and what indication led them to perceive a resident had experienced trauma. We analyzed data using content analysis (open-ended questions) and regression analyses (closed-ended questions). RESULTS: Three thousand seven hundred and sixty five care aides responded (70% response rate) to the survey, and 53% perceived caring for one or more residents with a history of psychological trauma in the previous 2 weeks. Within six categories of traumatic events, abuse (35%) and war exposure (26%) were most common. Most common indications of trauma reported by care aides (five categories) were reliving the experience or having intrusive symptoms (28%) and avoidant behaviors (24%). Care aides were more likely to report caring for a resident who they perceived had experienced past psychological trauma if they were younger, spoke English as their first language, self-reported experiencing more aggression from residents, or who worked in not-for-profit homes. CONCLUSIONS: This preliminary study supports the need for further study of care aides' perceptions and experiences of caring for residents with past trauma, and the effects of caring for these residents on quality of work life.

This Was My Crimean War: COVID-19 Experiences of Nursing Home Leaders.

OBJECTIVE: To describe professional and personal experiences of nursing home care leaders during early waves of the COVID-19 pandemic. DESIGN: Qualitative interpretive description. SETTING AND PARTICIPANTS: Eight sites across 2 Canadian provinces. Sites varied by COVID-19 status (low or high), size (<120 or ≥120 beds), and ownership model (for-profit or not-for-profit). We recruited 21 leaders as participants: 14 managers and 7 directors of care. METHODS: Remote Zoom-assisted semi-structured interviews conducted from January to April 2021. Concurrent data generation and inductive content analysis occurred throughout. Sampling ceased once we reached sufficient analytic variation and richness to answer research questions. RESULTS: Most participants were female, ≥50 years of age, and born in Canada. We found 4 major themes. (1) Responsibility to protect: Extreme precautions were employed to protect residents, staff, and leaders' families. Leaders experienced profound distress when COVID-19 infiltrated their care homes. (2) Overwhelming workloads: Changing public health orders and redeployment to pandemic-related activities caused administrative chaos. Leaders worked double shifts to cope with pandemic demands and maintain their usual work. (3) Mental and emotional toll: All participants reported symptoms of anxiety, depression, and insomnia, leading to ongoing exhaustion. Shifting staff focus from caring to custodial enforcement of isolation caused considerable distress, guilt, and grief. (4) Moving forward: The pandemic spotlighted deficiencies in the nursing home context that lead to inadequate quality of resident care and staff burnout. Some leaders indicated their pandemic experience signaled an unanticipated end to their careers. CONCLUSIONS AND IMPLICATIONS: Nursing home leaders faced mental distress and inordinate workloads during the pandemic. This is an urgent call for systemic change to improve working conditions for leaders and quality of care and quality of life for residents. Nursing home leaders are at increased risk of burnout, which must be addressed to mitigate attrition in the sector.

Behavioral Tests for Mouse Models of Autism: An Argument for the Inclusion of Cerebellum-Controlled Motor Behaviors.

Mouse models of Autism Spectrum Disorder (ASD) have been interrogated using a variety of behavioral tests in order to understand the symptoms of ASD. However, the hallmark behaviors that are classically affected in ASD - deficits in social interaction and communication as well as the occurrence of repetitive behaviors - do not have direct murine equivalents. Thus, it is critical to identify the caveats that come with modeling a human disorder in mice. The most commonly used behavioral tests represent complex cognitive processes based on largely unknown brain circuitry. Motor impairments provide an alternative, scientifically rigorous approach to understanding ASD symptoms. Difficulties with motor coordination and learning - seen in both patients and mice - point to an involvement of the cerebellum in ASD pathology. This brain area supports types of motor learning that are conserved throughout vertebrate evolution, allowing for direct comparisons of functional abnormalities between humans with autism and ASD mouse models. Studying simple motor behaviors provides researchers with clearly interpretable results. We describe and evaluate methods used on mouse behavioral assays designed to test for social, communicative, perseverative, anxious, nociceptive, and motor learning abnormalities. We comment on the effectiveness and validity of each test based on how much information its results give, as well as its relevance to ASD, and will argue for an inclusion of cerebellum-supported motor behaviors in the phenotypic description of ASD mouse models. LAY SUMMARY: Mouse models of Autism Spectrum Disorder help us gain insight about ASD symptoms in human patients. However, there are many differences between mice and humans, which makes interpreting behaviors challenging. Here, we discuss a battery of behavioral tests for specific mouse behaviors to explore whether each test does indeed evaluate the intended measure, and whether these tests are useful in learning about ASD.

Intrinsic Excitability Increase in Cerebellar Purkinje Cells after Delay Eye-Blink Conditioning in Mice.

Cerebellar-based learning is thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the downregulation of calcium-dependent SK-type K+ channels, which contribute to a medium-slow afterhyperpolarization (AHP) after spike bursts, regulating membrane excitability. In the hippocampus, intrinsic plasticity plays a role in trace eye-blink conditioning; however, corresponding excitability changes in the cerebellum in associative learning, such as in trace or delay eye-blink conditioning, are less well studied. Whole-cell patch-clamp recordings were obtained from Purkinje cells in cerebellar slices prepared from male mice ∼48 h after they learned a delay eye-blink conditioning task. Over a period of repeated training sessions, mice received either paired trials of a tone coterminating with a periorbital shock (conditioning) or trials in which these stimuli were randomly presented in an unpaired manner (pseudoconditioning). Purkinje cells from conditioned mice show a significantly reduced AHP after trains of parallel fiber stimuli and after climbing fiber evoked complex spikes. The number of spikelets in the complex spike waveform is increased after conditioning. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eye-blink conditioning, and point toward a downregulation of SK channels as a potential underlying mechanism. The observation that this learning effect lasts at least up to 2 d after training shows that intrinsic plasticity regulates excitability in the long term.SIGNIFICANCE STATEMENT Plasticity of membrane excitability ("intrinsic plasticity") has been observed in invertebrate and vertebrate neurons, coinduced with synaptic plasticity or in isolation. Although the cellular phenomenon per se is well established, it remains unclear what role intrinsic plasticity plays in learning and if it even persists long enough to serve functions in engram physiology beyond aiding synaptic plasticity. Here, we demonstrate that cerebellar Purkinje cells upregulate excitability in delay eye-blink conditioning, a form of motor learning. This plasticity is observed 48 h after training and alters synaptically evoked spike firing and integrative properties of these neurons. These findings show that intrinsic plasticity enhances the spike firing output of Purkinje cells and persists over the course of days.

SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces.

Neurons store information by changing synaptic input weights. In addition, they can adjust their membrane excitability to alter spike output. Here, we demonstrate a role of such "intrinsic plasticity" in behavioral learning in a mouse model that allows us to detect specific consequences of absent excitability modulation. Mice with a Purkinje-cell-specific knockout (KO) of the calcium-activated K+ channel SK2 (L7-SK2) show intact vestibulo-ocular reflex (VOR) gain adaptation but impaired eyeblink conditioning (EBC), which relies on the ability to establish associations between stimuli, with the eyelid closure itself depending on a transient suppression of spike firing. In these mice, the intrinsic plasticity of Purkinje cells is prevented without affecting long-term depression or potentiation at their parallel fiber (PF) input. In contrast to the typical spike pattern of EBC-supporting zebrin-negative Purkinje cells, L7-SK2 neurons show reduced background spiking but enhanced excitability. Thus, SK2 plasticity and excitability modulation are essential for specific forms of motor learning.

Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule.

KEY POINTS: Spike doublets comprise ∼10% of in vivo complex spike events under spontaneous conditions and ∼20% (up to 50%) under evoked conditions. Under near-physiological slice conditions, single complex spikes do not induce parallel fibre long-term depression. Doublet stimulation is required to induce long-term depression with an optimal parallel-fibre to first-complex-spike timing interval of 150 ms. ABSTRACT: The classic example of biological supervised learning occurs at cerebellar parallel fibre (PF) to Purkinje cell synapses, comprising the most abundant synapse in the mammalian brain. Long-term depression (LTD) at these synapses is driven by climbing fibres (CFs), which fire continuously about once per second and therefore generate potential false-positive events. We show that pairs of complex spikes are required to induce LTD. In vivo, sensory stimuli evoked complex-spike doublets with intervals ≤150 ms in up to 50% of events. Using realistic [Ca2+ ]o and [Mg2+ ]o concentrations in slices, we determined that complex-spike doublets delivered 100-150 ms after PF stimulus onset were required to trigger PF-LTD, which is consistent with the requirements for eyeblink conditioning. Inter-complex spike intervals of 50-150 ms provided optimal decoding. This stimulus pattern prolonged evoked spine calcium signals and promoted CaMKII activation. Doublet activity may provide a means for CF instructive signals to stand out from background firing.

Toward a Neurocentric View of Learning.

Synaptic plasticity (e.g., long-term potentiation [LTP]) is considered the cellular correlate of learning. Recent optogenetic studies on memory engram formation assign a critical role in learning to suprathreshold activation of neurons and their integration into active engrams ("engram cells"). Here we review evidence that ensemble integration may result from LTP but also from cell-autonomous changes in membrane excitability. We propose that synaptic plasticity determines synaptic connectivity maps, whereas intrinsic plasticity-possibly separated in time-amplifies neuronal responsiveness and acutely drives engram integration. Our proposal marks a move away from an exclusively synaptocentric toward a non-exclusive, neurocentric view of learning.

Calcium threshold shift enables frequency-independent control of plasticity by an instructive signal.

At glutamatergic synapses, both long-term potentiation (LTP) and long-term depression (LTD) can be induced at the same synaptic activation frequency. Instructive signals determine whether LTP or LTD is induced, by modulating local calcium transients. Synapses maintain the ability to potentiate or depress over a wide frequency range, but it remains unknown how calcium-controlled plasticity operates when frequency variations alone cause differences in calcium amplitudes. We addressed this problem at cerebellar parallel fiber-Purkinje cell synapses, which can undergo LTD or LTP in response to 1-Hz and 100-Hz stimulation. We observed that high-frequency activation elicits larger spine calcium transients than low-frequency stimulation under all stimulus conditions, but, regardless of activation frequency, climbing fiber (CF) coactivation provides an instructive signal that further enhances calcium transients and promotes LTD. At both frequencies, buffering calcium prevents LTD induction and LTP results instead, identifying the enhanced calcium signal amplitude as the critical parameter contributed by the instructive CF signal. These observations show that it is not absolute calcium amplitudes that determine whether LTD or LTP is evoked but, instead, the LTD threshold slides, thus preserving the requirement for relatively larger calcium transients for LTD than for LTP induction at any given stimulus frequency. Cerebellar LTD depends on the activation of calcium/calmodulin-dependent kinase II (CaMKII). Using genetically modified (TT305/6VA and T305D) mice, we identified α-CaMKII inhibition upon autophosphorylation at Thr305/306 as a molecular event underlying the threshold shift. This mechanism enables frequency-independent plasticity control by the instructive CF signal based on relative, not absolute, calcium thresholds.

Asymmetries in Cerebellar Plasticity and Motor Learning.

Synaptic plasticity at the parallel fiber to Purkinje cell synapse has long been considered a cellular correlate for cerebellar motor learning. Functionally, long-term depression and long-term potentiation at these synapses seem to be the reverse of each other, with both pre- and post-synaptic expression occurring in both. However, different cerebellar motor learning paradigms have been shown to be asymmetric and not equally reversible. Here, we discuss the asymmetric reversibility shown in the vestibulo-ocular reflex and eyeblink conditioning and suggest that different cellular plasticity mechanisms might be recruited under different conditions leading to unequal reversibility.

Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning--a form of cerebellum-dependent motor learning--is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres--a model for activity-dependent synaptic pruning--is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.

Motor learning in the VOR: the cerebellar component.

This paper reviews results that support a model in which memory for VOR gain is initially encoded in the flocculus, and in which cerebellar LTD and LTP are responsible for gain increases and gain decreases, respectively. We also review data suggesting that after it is encoded, motor memory can either be disrupted, possibly by a local mechanism, or else consolidated. We show that consolidation can be rapid, in which case the frequency dependence of learning is unchanged and we will argue that this is consistent with a local mechanism of consolidation. In the longer term, however, the available evidence supports the transfer of memory out of the flocculus. In new experiments reported here, we address the mechanism of memory encoding. Pharmacological evidence shows that both mGluR1 and GABA(B) receptors in the flocculus are necessary for gain-up, but not for gain-down learning. Immunohistochemical experiments show that the two receptors are largely segregated on different dendritic spines on Purkinje cells. Together with what is already known of the mechanisms of cerebellar LTD and LTP, our data suggest that the direction of learning may be determined by interactions among groups of spines. Our results also provide new evidence for the existence of frequency channels for vestibular signals within the cerebellar cortex.

The bidirectionality of motor learning in the vestibulo-ocular reflex is a function of cerebellar mGluR1 receptors.

Bidirectional changes in synaptic transmission have the potential to optimize the control of movement. However, it can be difficult to establish a causal relationship between the bidirectionality of synaptic plasticity and bidirectional changes in the speed of actual movements. We asked whether metabotropic glutamate receptor 1 (mGluR1) receptors, which participate in cerebellar long-term depression (LTD), are necessary for bidirectional motor learning in the vestibulo-ocular reflex (VOR). Cerebellar LTD and long-term potentiation (LTP) are thought to cause increases and decreases, respectively, in the gain of the VOR; the direction of learning depends on the behavioral protocol. We injected either the mGluR1 agonist (S)-DHPG or the antagonist YM 298198 bilaterally into the flocculus of alert cats, and then induced motor learning. In the presence of YM 298198, the VOR gain decreased in gain-up, as well as in gain-down protocols. (S)-DHPG augmented gain-up learning. Gain-down learning was not significantly affected by either drug. These results supported the hypothesis that gain-up learning relies on cerebellar LTD, but gain-down learning relies on a different mechanism. In the absence of mGluR1 activity, cerebellar LTD may be replaced with LTP, permitting learning in only one direction.

Consolidation and disruption of motor memory generalize across stimulus conditions in the vestibulo-ocular reflex.

The vestibulo-ocular reflex (VOR) exhibits motor learning that initially depends on synaptic plasticity in the cerebellar cortex. Learned decreases in VOR gain can be disrupted by rotation in darkness immediately following learning, but consolidate rapidly if the disruption stimulus is delayed. Disruption may simply reverse the synaptic changes that have recently occurred, or it may reflect new learning at other sites. The alternative to disruption, rapid consolidation, also may take place by altering the existing memory trace or may require changes at other locations. To test these possibilities, we induced decreases in the gain of the VOR in cats that wore miniaturizing goggles. Using a range of frequencies of rotation, we investigated the patterns of generalization for disruption and for rapid consolidation of the learned changes in gain. Learning was most effective at the particular frequencies that were used during training. However, disruption and rapid consolidation were not more effective at the rotation frequencies that were used during training. Instead, after consolidation, the memory retained the frequency tuning that had been established during the learning process. We conclude that disruption and rapid consolidation may not require new learning.

Rapid consolidation of motor memory in the vestibuloocular reflex.

Motor memory is relatively labile immediately after learning but can become more stable through consolidation. We investigated consolidation of motor memory in the vestibuloocular reflex (VOR). Cats viewed the world through telescopic lenses during 60 min of passive rotation. Learned decreases (gain-down learning) and increases in the VOR gain (gain-up learning) were measured during sinusoidal rotation at 2 Hz. We found that if rotation in darkness immediately followed learning, the gain of the VOR reverted toward its prelearning value, indicating that expression of the memory was disrupted. If after gain-down learning the cat spent another 60 min stationary without form vision, subsequent disruption did not occur, suggesting that memory had consolidated. Consolidation was less robust for gain-up learning. We conclude that memory in the VOR is initially labile but consolidates rapidly and consistently after gain-down learning.