Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Artificial intelligence: An eye cast towards the mental health nursing horizon

© 2023 The Authors.There has been an international surge towards online, digital, and telehealth mental health services, further amplified during COVID-19. Implementation and integration of technological innovations, including artificial intelligence (AI), have increased with the intention to improve clinical, governance, and administrative decision-making. Mental health nurses (MHN) should consider the ramifications of these changes and reflect on their engagement with AI. It is time for mental health nurses to demonstrate leadership in the AI mental health discourse and to meaningfully advocate that safety and inclusion of end users' of mental health service interests are prioritized. To date, very little literature exists about this topic, revealing limited engagement by MHNs overall. The aim of this article is to provide an overview of AI in the mental health context and to stimulate discussion about the rapidity and trustworthiness of AI related to the MHN profession. Despite the pace of progress, and personal life experiences with AI, a lack of MHN leadership about AI exists. MHNs have a professional obligation to advocate for access and equity in health service distribution and provision, and this applies to digital and physical domains. Trustworthiness of AI supports access and equity, and for this reason, it is of concern to MHNs. MHN advocacy and leadership are required to ensure that misogynist, racist, discriminatory biases are not favoured in the development of decisional support systems and training sets that strengthens AI algorithms. The absence of MHNs in designing technological innovation is a risk related to the adequacy of the generation of services that are beneficial for vulnerable people such as tailored, precise, and streamlined mental healthcare provision. AI developers are interested to focus on person-like solutions; however, collaborations with MHNs are required to ensure a person-centred approach for future mental healthcare is not overlooked

Acute Ethanol Effects on Focal Cerebral Ischemia in Nonfasted Rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66417/1/j.1530-0277.1997.tb03832.x.pd

Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

<p>Abstract</p> <p>Background</p> <p>Most patients with ovarian cancer are diagnosed with advanced stage disease (<it>i.e</it>., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis.</p> <p>Methods</p> <p>The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups.</p> <p>Results</p> <p>A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: <it>SSBP1</it>, <it>IFI6 DDT</it>, <it>IFI27</it>, <it>C11orf92</it>, <it>NFKBIA</it>, <it>TNXB</it>, <it>NEAT1 </it>and <it>TFG </it>were up-regulated while another group of genes consisting of: <it>LAMB2</it>, <it>XRCC6</it>, <it>MEF2C</it>, <it>RBM5</it>, <it>FOXP1</it>, <it>NUDCP2</it>, <it>LGALS3</it>, <it>TMEM185A</it>, and <it>C1S </it>were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as <it>DDAH2, RNase K and TCEAL2 </it>might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such as <it>RNase K, FOXP1</it>, <it>LAMB2 </it>and <it>MRVI1 </it>were up-regulated.</p> <p>Conclusion</p> <p>The DEGs in patients with stage III serous ovarian cancer were successfully and reliably identified by the ACP-based RT PCR technique. The DEGs identified in this study might help predict the prognosis of patients with stage III serous ovarian cancer as well as suggest targets for the development of new treatment regimens.</p

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

<p>Abstract</p> <p>Background</p> <p>Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging.</p> <p>Methods</p> <p>Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations.</p> <p>Results</p> <p>Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race.</p> <p>Conclusion</p> <p>The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.</p

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’ ’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. Conclusions/Significance: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that

Pre-attentive processing in children with early and continuously-treated PKU. Effects of concurrent Phe level and lifetime dietary control

Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual’s responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure

Variation in MSRA Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis

Meconium ileus (MI), a life-threatening intestinal obstruction due to meconium with abnormal protein content, occurs in approximately 15 percent of neonates with cystic fibrosis (CF). Analysis of twins with CF demonstrates that MI is a highly heritable trait, indicating that genetic modifiers are largely responsible for this complication. Here, we performed regional family-based association analysis of a locus that had previously been linked to MI and found that SNP haplotypes 5′ to and within the MSRA gene were associated with MI (P = 1.99×10−5 to 1.08×10−6; Bonferroni P = 0.057 to 3.1×10−3). The haplotype with the lowest P value showed association with MI in an independent sample of 1,335 unrelated CF patients (OR = 0.72, 95% CI [0.53–0.98], P = 0.04). Intestinal obstruction at the time of weaning was decreased in CF mice with Msra null alleles compared to those with wild-type Msra resulting in significant improvement in survival (P = 1.2×10−4). Similar levels of goblet cell hyperplasia were observed in the ilea of the Cftr−/− and Cftr−/−Msra−/− mice. Modulation of MSRA, an antioxidant shown to preserve the activity of enzymes, may influence proteolysis in the developing intestine of the CF fetus, thereby altering the incidence of obstruction in the newborn period. Identification of MSRA as a modifier of MI provides new insight into the biologic mechanism of neonatal intestinal obstruction caused by loss of CFTR function

Models of Traumatic Cerebellar Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective