RESUMO
The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.
Assuntos
Gânglios da Base/citologia , Córtex Cerebral/citologia , Vias Neurais , Neurônios/citologia , Tálamo/citologia , Animais , Gânglios da Base/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tálamo/anatomia & histologiaRESUMO
AIM: To identify current perceptions of aducanumab among patients with Alzheimer's disease (AD) and their caregivers. METHODS: A total of 352 caregivers of AD patients seen at Hawaii's largest multidisciplinary neuroscience center between January 01, 2019, and June 21, 2021, were surveyed by telephone to understand patient and caregiver knowledge, familiarity, and hesitancy toward aducanumab. RESULTS: Thirty-seven percent of caregivers were familiar with aducanumab. Caregivers who were spouses of their respective patients with AD (p=0.0023) had increased odds of familiarity. Additional predictors of aducanumab familiarity included patients with higher mini-mental state examination scores (p=0.0076) and those who received mental stimulation (p=0.007). Conversely, caregivers who identified as native Hawaiian and other Pacific Islanders (NHPI) (p=0.044) or the patient's child (p=0.010) were predictors of decreased familiarity. Only 33% of caregivers familiar with aducanumab believed it to be safe and 56% reported "side effects" as their top concern. Thirty percent of caregivers were moderately ready or very ready to use aducanumab if given the opportunity. CONCLUSION: Most caregivers of Hawaii AD patients were unfamiliar with aducanumab. Furthermore, those familiar were hesitant to trial the medication. Improved education and awareness of AD therapies are important, so families and caregivers of AD patients can make more informed decisions regarding AD treatment.
RESUMO
The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.
Assuntos
Potenciais de Ação/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Medo/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Algoritmos , Animais , Complexo Nuclear Basolateral da Amígdala/citologia , Medo/psicologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Rede Nervosa/citologia , Optogenética/métodosRESUMO
The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical input arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. Here, we construct a comprehensive map of all cortico-tectal projections and identify four collicular zones with differential cortical inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) and lateral (SC.l). Further, we delineate the distinctive brain-wide input/output organization of each collicular zone, assemble multiple parallel cortico-tecto-thalamic subnetworks, and identify the somatotopic map in the SC that displays distinguishable spatial properties from the somatotopic maps in the neocortex and basal ganglia. Finally, we characterize interactions between those cortico-tecto-thalamic and cortico-basal ganglia-thalamic subnetworks. This study provides a structural basis for understanding how SC is involved in integrating different sensory modalities, translating sensory information to motor command, and coordinating different actions in goal-directed behaviors.