Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum

Cardiovascular risk factors and cardiac surgery outcomes in a multiethnic sample of men and women

BACKGROUND: Cardiovascular disease is more prevalent in some ethnic groups than in others, as are risk factors stemming from cultural practices and values. Data on the health status of Asians and Pacific Islanders are scarce and sporadic, and data on the 2 groups are usually combined for analysis. OBJECTIVE: To determine ethnic and sex-related differences among white, Japanese, and Pacific Island subjects in cardiovascular risk factors and outcomes after coronary artery bypass graft surgery. METHODS: Data were collected from a random sample of 41 men and 19 women scheduled for nonemergent coronary artery bypass graft surgery: 19 white, 18 Japanese, and 23 Pacific Island/Hawaiian subjects. Subjects were interviewed about risk factors before surgery and were followed up for the first 20 hours after surgery. Problems that occurred during the remainder of the hospital stay were assessed by chart review. Instruments used included the Charlson Comorbidity Index, Acute Physiology and Chronic Health Evaluation II, and the Therapeutic Intervention Scoring System. RESULTS: Pacific Island and Japanese subjects differed significantly in their demographic and clinical characteristics. Pacific Islanders tended to have a more difficult postoperative course than did white subjects, whereas Japanese patients tended to have fewer problems and an easier postoperative course than other subjects. CONCLUSIONS: Further study of ethnic variations in risk factors and surgical outcomes, especially variations in comorbidities, age at the onset of signs and symptoms, and postoperative complications, is needed. Combining data obtained from Japanese and Pacific Island subjects for data analysis most likely will result in a loss of important information.</jats:p