A Computational Model for the Simulation of Prepulse Inhibition and Its Modulation by Cortical and Subcortical Units.

The sensorimotor gating is a nervous system function that modulates the acoustic startle response (ASR). Prepulse inhibition (PPI) phenomenon is an operational measure of sensorimotor gating, defined as the reduction of ASR when a high intensity sound (pulse) is preceded in milliseconds by a weaker stimulus (prepulse). Brainstem nuclei are associated with the mediation of ASR and PPI, whereas cortical and subcortical regions are associated with their modulation. However, it is still unclear how the modulatory units can influence PPI. In the present work, we developed a computational model of a neural circuit involved in the mediation (brainstem units) and modulation (cortical and subcortical units) of ASR and PPI. The activities of all units were modeled by the leaky-integrator formalism for neural population. The model reproduces basic features of PPI observed in experiments, such as the effects of changes in interstimulus interval, prepulse intensity, and habituation of ASR. The simulation of GABAergic and dopaminergic drugs impaired PPI by their effects over subcortical units activity. The results show that subcortical units constitute a central hub for PPI modulation. The presented computational model offers a valuable tool to investigate the neurobiology associated with disorder-related impairments in PPI.

Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments.

The forced swim test (FST) is widely used to evaluate the antidepressant-like activity of compounds and is sensitive to stimuli that cause depression-like behaviors in rodents. The immobility behavior observed during the test has been considered to represent behavioral despair. In addition, some studies suggest that the FST impairs rats' performance on cognitive tests, but these findings have rarely been explored. Thus, we investigated the effects of the FST on behavioral tests related to neuropsychiatric diseases that involve different cognitive components: novel object recognition (NOR), the object location test (OLT) and prepulse inhibition (PPI). Brain-derived neurotrophic factor (BDNF) levels in the frontal cortex and hippocampus were evaluated. The rats were forced to swim twice (15-min session followed by a 5-min session 24h later) and underwent cognitive tests 24h after the last swimming exposure. The FST impaired the rats' performance on the OLT and reduced the PPI and acoustic startle responses, whereas the NOR was not affected. The cognitive impairments were not correlated with an immobility behavior profile, but a significant negative correlation between the frontal BDNF levels and immobility behavior was identified. These findings suggest a protective role of BDNF against behavioral despair and demonstrate a deleterious effect of the FST on spatial memory and pre-attentive processes, which point to the FST as a tool to induce cognitive impairments analogous to those observed in depression and in other neuropsychiatric disorders.

Sistema automático de análise comportamental em pombos / Automatic behavioral analysis system in pigeons

Este trabalho apresenta o projeto e os testes de um equipamento para registro automatizado da amplitude e da latência da resposta de sobressalto acústico em pombos. O sistema desenvolvido é formado por uma câmara experimental, com uma célula de carga acoplada ao piso para ser utilizada como sensor de força, circuitos para geração de estímulos (luz, som ou choque) e circuitos de condicionamento e interfaceamento dos sinais a um microcomputador utilizado para controle, armazenamento e análise dos dados. O software para controle do sistema foi desenvolvido utilizando-se linguagem C para operar em plataformas DOS ou Windows, com rotinas de controle para o protocolo experimental (número, duração e taxa de repetição dos estímulos) e rotinas gráficas para apresentar as curvas de amplitude da resposta em relação ao tempo, armazenamento dos dados no disco e processamento. Os dados são armazenados em arquivos e podem ser analisados estatisticamente com outros aplicativos computacionais. Foram realizados testes comportamentais com pombos e ratos, expostos a 20 estímulos sonoros (1 kHz, 100 dBA, duração de 1 s e taxa de repetição de 30 s). Os animais do grupo controle permaneceram na caixa durante 30 minutos sem receber estímulos. A amplitude do sobressalto, medida em kgf, foi registrada durante 4 s e analisada em janelas temporais de 1 s imediatamente após o som. Os testes com ratos apresentaram resultados semelhantes aos da literatura e indicaram a eficiência do sistema. Comparativamente aos ratos, os pombos apresentaram menor amplitude e maior latência e indicaram diferenças comportamentais entre as duas espécies. O equipamento mostrou-se adequado para as investigações neurobiológicas e comportamentais que usam modelos animais.

This work presents the design and testing of an apparatus for automatic recording of the magnitude and latency of acoustic startle response in pigeons. This system includes one experimental chamber with a load cell coupled to its floor (which is used as a force sensorto measure the amplitude of the response to the stimulus), stimuli generation circuits (light, sound or shock) and interfacing circuits (to a microcomputer that is used for control, storage and data analysis). The software used to control the system was developed using C language and runs under DOS or Windows operational systems. There are routines to implement the experimental protocol (number, duration and repetition rate of stimuli) and graphics routines to show the amplitude of the startle response curves as a function of time. The data may be saved in the disk for further statistical analysis with other programs. Behavioral tests with exposure to 20 tone-pulses (1 kHz, 100 dBA, 1 s, every 30 s) were carried out with pigeons and rats. The control group animals remained in the chamber during 30 min without receiving any acoustic stimulation. The magnitude of startle was recorded (in kgf) during 4 s andanalyzed in temporal windows of 1 s. The tests with rats corroborate the literature and indicate the efficiency of the system. Compared to rats, the pigeons presented lower magnitude and longer latency of acoustic response, indicating behavioral differences between the two species. The equipment was considered adequate for neurobiological and behavioral investigations which use automatic recording of acoustic stimuli responses.