Stimulation of Midbrain Dopaminergic Structures Modifies Firing Rates of Rat Lateral Habenula Neurons

Ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) are midbrain structures known to be involved in mediating reward in rodents. Lateral habenula (LHb) is considered as a negative reward source and it is reported that stimulation of the LHb rapidly induces inhibition of firing in midbrain dopamine neurons. Interestingly, the phasic fall in LHb neuronal activity may follow the excitation of dopamine neurons in response to reward-predicting stimuli. The VTA and SNpc give rise to dopaminergic projections that innervate the LHb, which is also known to be involved in processing painful stimuli. But it's unclear what physiological effects these inputs have on habenular function. In this study we distinguished the LHb pain-activated neurons of the Wistar rats and assessed their electrophysiological responsiveness to the stimulation of the VTA and SNpc with either single-pulse stimulation (300 µA, 0.5 Hz) or tetanic stimulation (80 µA, 25 Hz). Single-pulse stimulation that was delivered to either midbrain structure triggered transient inhibition of firing of ∼90% of the LHb pain-activated neurons. However, tetanic stimulation of the VTA tended to evoke an elevation in neuronal firing rate. We conclude that LHb pain-activated neurons can receive diverse reward-related signals originating from midbrain dopaminergic structures, and thus participate in the regulation of the brain reward system via both positive and negative feedback mechanisms

Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research

Measuring Empathizing and Systemizing with a Large US Sample

A large number of people completed one of two versions of the empathizing quotient (EQ) and systemizing quotient (SQ). One version had the negatively phrased items all re-worded. These re-worded items were answered more rapidly than the original items, and for the SQ produced a more reliable scale. Subjects gave self-assessments of empathizing and systemizing, and these were moderately correlated, r≈.6, with their respective quotients. Females had on average higher empathizing scores and males had on average higher systemizing scores. If a female-male pair was chosen at random, the female would have the higher empathizing score about two-thirds of the time, and the males would have the higher systemizing score about two-thirds of the time

Neuroanatomical Study of the A11 Diencephalospinal Pathway in the Non-Human Primate

BACKGROUND: The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP. METHODS AND FINDINGS: In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. CONCLUSION: The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells

Predictive ability of regression models. Part I: Standard Deviation of Prediction Errors (SDEP)

he standard deviation of prediction errors (SDEP) is used to evaluate and compare the predictive ability of some regression models, namely MLR, ACE and linear and non-linear PLS, the last being the best one. The parameter is determined by a cross-validation approach as an average of several runs obtained on forming groups in a random way. The variation in SDEP with the number of latent variables in PLS is also discussed