Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.

Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons

Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.

Methcathinone Increases Visually-evoked Neuronal Activity and Enhances Sensory Processing Efficiency in Mice

Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused worldwide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and empathy.However,little is known about how MCAT modulates neuronal activity in vivo.Here,we evaluated the effect of MCAT on neuronal activity with a series of functional approaches.C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold,especially in sensory and motor cortices,striatum,and midbrain motor nuclei.In vivo single-unit recording and two-photon Ca^(2+) imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration.Notably,MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability,specifically during a natural movie stimulus.It improved the information-processing efficiency by enhancing the single-neuron coding capacity,suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.

Effects of pentobarbital anesthesia on nociceptive processing in the medial and lateral pain pathways in rats

Objective To investigate the effects of pentobarbital anesthesia on nociceptive processing in the medial and lateral pain pathways.Methods Laser stimulation was employed to evoke nociceptive responses in rats under awake or anesthetic conditions.Pain-related neuronal activities were simultaneously recorded from the primary somatosensory cortex （SI） ,ventral posterolateral thalamus （VPL） ,anterior cingulate cortex （ACC） ,and medial dorsal thalamus （MD） with 4 eight-wire microelec-trode arrays.Results Compared with the awake state,pentobarbital anesthesia significantly suppressed the neural activities induced by noxious laser stimulation.Meanwhile,the pain-evoked changes in the neuronal correlations between cortex and thalamus were suppressed in both medial and lateral pain pathways.In addition,the spontaneous firing rates in all the 4 areas were altered （including inhibition and excitation） under the condition of anesthesia.Conclusion The nociceptive processing in the brain can be dramatically changed by anesthesia,which indicates that there are considerable differences in the brain activities between awake and anesthetized states.It is better to employ awake animals for recording neural activity when investigating the sensory coding mechanisms,especially pain coding,in order to obtain data that precisely reflect the physiological state.

Contributions of distinct prefrontal neuron classes in reward processing

The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(putative pyramidal cells and interneurons)in the PFC played different functional roles in neural circuits involved in forming working memory and abstract categories.However,it remains elusive how the two types of neurons process reward information in the PFC.To investigate this issue,the activity of single neurons was extracellularly recorded in the PFC of the monkey performing a reward predicting task.PFC neurons were classified into putative pyramidal cells and interneurons,respectively,based on the waveforms of action potentials.Both the two types of neurons encoded reward information and discriminated two reward conditions(the preferred reward condition vs.the nonpreferred reward condition).However,the putative pyramidal neurons had better and more reliable discriminability than the putative interneurons.Also,the pyramidal cells represented reward information in the preferred reward condition,but not in the nonpreferred reward condition by raising their firing rates relative to the baseline rates.In contrast,the interneurons encoded reward information in the nonpreferred reward condition,but not in the preferred reward condition by inhibiting their discharge rates relative to the baseline rates.These results suggested that the putative pyramidal cells and interneurons had complementary functions in reward processing.These findings may help to clarify individual functions of each type of neurons in PFC neuronal circuits involved in reward processing.