Humans and animals have a fundamental ability to use experiences and environmental information to organize behavior. It often happens that humans and animals make decisions and prepare actions under uncertain situations. Uncertainty would significantly affect the state of animals' minds, but may not be reflected in behavior. How to "read animals' mind state" under different situations is a challenge. Here, we report that neuronal activity in the medial prefrontal cortex (mPFC) of rats can reflect the environmental uncertainty when the task situation changes from certain to uncertain. Rats were trained to perform behavioral tasks under certain and uncertain situations. Under certain situations, rats were required to simply repeat two nose-poking actions that each triggered short auditory tone feedback (single-task situation). Whereas under the uncertain situation, the feedback could randomly be either the previous tone or a short musical rhythm. No additional action was required upon the music feedback, and the same secondary nose-poking action was required upon the tone feedback (dual-task situation); therefore, the coming task was uncertain before action initiation. We recorded single-unit activity from the mPFC when the rats were performing the tasks. We found that in the dual task, when uncertainty was introduced, many mPFC neurons were actively engaged in dealing with the uncertainty before the task initiation, suggesting that the rats could be aware of the task situation change and encode the information in the mPFC before the action of task initiation.
Animals ; Prefrontal Cortex/cytology* ; Uncertainty ; Neurons/physiology* ; Male ; Rats ; Rats, Long-Evans ; Action Potentials/physiology* ; Acoustic Stimulation

The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
Animals ; Neurons/physiology* ; Mice ; Prefrontal Cortex/cytology* ; Parvalbumins/metabolism* ; Brain Mapping/methods* ; Neural Pathways/physiology* ; Somatostatin/metabolism* ; Male ; Interneurons/physiology* ; Mice, Inbred C57BL ; Thalamus/physiology* ; Mice, Transgenic

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.
Animals ; Glutamic Acid ; physiology ; Male ; Mental Recall ; physiology ; Mice, Inbred C57BL ; Neural Pathways ; cytology ; physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons ; physiology ; Prefrontal Cortex ; cytology ; physiology ; Spatial Memory ; physiology ; Temporal Lobe ; cytology ; physiology

OBJECTIVETo investigate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) of normal and 6-OHDA-lesioned rats and the responses of the neurons to 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation.

METHODSThe changes in spontaneous firing of the pyramidal neurons in the mPFC in response to 5-HT(7) receptor stimulation were observed by extracellular recording in normal and 6-OHDA-lesioned rats.

RESULTSBoth systemic and local administration of 5-HT(7) receptor agonist AS 19 resulted in 3 response patterns (excitation, inhibition and no change) of the pyramidal neurons in the mPFC of normal and 6-OHDA-lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAA receptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the ?ring rate of the neurons in the lesioned rats.

CONCLUSIONThe activity of mPFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.

Action Potentials ; Animals ; Oxidopamine ; Parkinson Disease ; metabolism ; Prefrontal Cortex ; cytology ; Pyramidal Cells ; drug effects ; Rats ; Receptors, Serotonin ; metabolism ; Serotonin Receptor Agonists ; pharmacology

OBJECTIVETo study the effects of Citalopram on the mRNA expression of bax and bel-2 in frontal cortical neurons and on cell apoptosis of rats after stress.

METHODSTwenty-four healthy male SD rats were randomly divided into three groups (n = 8). The control group did no receive any treatment, the stress group was subject to stress and given normal saline and experimental group was given Citalopram irrigation stomach after stress. Rats were forced to swim to establish chronic stress model (15 min/d, 4 weeks), bax, bcl-2 mRNA expression were tested by in situ hybridization technique (ISH), TUNEL assay was used to determine cell apoptosis, Nikon image analysis software were used to measure the number of positive cells in each index.

RESULTSCompared with the control group, the stress group showed a larger number of bax mRNA expressing cells( P < 0.01), a smaller number of bcl-2 mRNA expressing cells (P < 0.01), and the staining intensity of positive cells was significantly reduced( P < 0.01). Compared with the stress group, the experiment group showed more reduced number of bax mRNA positive cells( P < 0.01) and significantly increased bcl-2 mRNA positive cells( P < 0.05), a small amount of positive cells were found, compared with that in the stress group, nuclear condensation in the experimental group was reduced significantly and the staining was obviously weaker( P < 0.01).

CONCLUSIONCitalopram significantly antagonizes bax mRNA and potentiatesbcl-2 mRNA protein expression and inhibits apoptosis of rat prefrontal cortical neurons caused by chronic stress, which might be one possible mechanism of Citalopram for prevention and treatment of psychosis caused by chronic stress.

Animals ; Apoptosis ; Citalopram ; pharmacology ; Male ; Neurons ; drug effects ; metabolism ; Prefrontal Cortex ; cytology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury.

METHODThe synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process.

RESULTACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus.

CONCLUSIONThe synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.

Acetylcholine ; metabolism ; Animals ; Choline ; metabolism ; Extracellular Fluid ; drug effects ; metabolism ; Hippocampus ; cytology ; Male ; Neurotransmitter Agents ; metabolism ; Perfusion ; Prefrontal Cortex ; cytology ; Rats ; Rats, Sprague-Dawley ; Sodium Azide ; administration & dosage ; pharmacology ; Time Factors

The present study is aimed to investigated the firing activity of pyramidal neurons and interneurons in the medial prefrontal cortex (mPFC) in rats with bilateral intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) by using in vivo extracellular recording. The results showed that the injection of 5,7-DHT reduced the 5-hydroxytryptamine (5-HT) levels in the mPFC and dorsal raphe nucleus in the rats. The firing rate of mPFC pyramidal neurons in rats with 5,7-DHT injection was significantly higher than that of normal rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing, while the injection decreased the firing rate of mPFC interneurons and changed the firing pattern of the interneurons towards a more irregular. These results indicate that the lesions of the serotonergic neurons lead to the changes in the firing activity of mPFC pyramidal neurons and interneurons, suggesting that serotonergic system plays an important role in the regulation of the neuronal activity in the mPFC.
5,7-Dihydroxytryptamine ; pharmacology ; Action Potentials ; Animals ; Dorsal Raphe Nucleus ; cytology ; Injections, Intraventricular ; Interneurons ; drug effects ; Prefrontal Cortex ; cytology ; Pyramidal Cells ; drug effects ; Rats ; Serotonin ; metabolism

The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli make addiction hard to cure by contributing to cocaine seeking and relapse. So it's of great importance to examine the neurobiological basis of addiction memory. Cocaine conditioned place preference (CPP) used in this study is a form of Pavlovian conditioning which can establish associations between drug and contextual factors. c-Fos and Zif268 are commonly used immediate early gene (IEG) makers to identify neurons that are activated after a stimulus or behavioral conditioning. This study was designed to reveal neuronal c-Fos, Zif268 expression pattern in 10 brain regions following cocaine context-associated reward memory retrieval in mice, combining animal behavioral study and immunofluorescence method. C57BL/6 mice were randomly divided into 3 groups: Saline retrieval, Cocaine retrieval, and No retrieval of cocaine groups. Cocaine retrieval and No retrieval of cocaine underwent CPP training (one side paired with cocaine, and the other side with saline) except that No retrieval of cocaine group didn't undergo CPP test. Saline retrieval group received saline injections (i.p) on both sides. The results showed that: Neuronal c-Fos, Zif268 protein expression levels in nucleus accumbens (NAc) core both were elevated in Cocaine retrieval group compared with those in Saline retrieval (Control) group during cocaine context-associated reward memory retrieval. Zif268 protein expression level in basolateral amygdala (BLA) was also elevated in Cocaine retrieval group compared with that in control mice. Elevation was not seen in other regions such as hippocampus, prefrontal cortex (PFC). Thus, NAc core and BLA were activated during cocaine context-associated reward memory retrieval. The results suggest that neurons that are activated in NAc core and BLA are crucial basis of cocaine context-associated reward memory.
Animals ; Basolateral Nuclear Complex ; cytology ; Cocaine ; pharmacology ; Conditioning (Psychology) ; Early Growth Response Protein 1 ; metabolism ; Hippocampus ; Memory ; Mice ; Mice, Inbred C57BL ; Neurons ; metabolism ; Nucleus Accumbens ; metabolism ; Prefrontal Cortex ; Proto-Oncogene Proteins c-fos ; metabolism ; Reward

The α2A adrenoceptors (α2A-ARs) are the most common adrenergic receptor subtype found in the prefrontal cortex (PFC). It is generally accepted that stimulation of postsynaptic α2A-ARs on pyramidal neurons are key to PFC functions, such as working memory. However, the expression of α2A-ARs in interneurons is largely unknown. In the present study using double-labeling immunofluorencence technique, we investigated the expression of α2A-ARs in major types of rat PFC interneurons expressing calcium-binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). Our data demonstrated that α2A-ARs are highly expressed in calcium-binding protein immunoreactive interneurons of rat PFC, suggesting that stimulation of α2A-ARs may alter neural networks comprising pyramidal neurons and interneurons, thereby exerting a beneficial effect on PFC cognitive functions. The present study provides the morphological basis for a potential mechanism by which stimulation of α2A-ARs induces cognitive improvement.
Animals ; Calbindin 2 ; metabolism ; Calbindins ; metabolism ; Interneurons ; metabolism ; Parvalbumins ; metabolism ; Prefrontal Cortex ; cytology ; Rats ; Receptors, Adrenergic, alpha-2 ; metabolism

OBJECTIVETo study the effects of Ginkgo biloba extract 50 (GBE50) on inflammatory cytokines and glia cell injury in the prefrontal cortex and hippocampus of aging rats and its probable mechanism. Methods Totally 45 male SD rats were randomly divided into 4 groups, i.e., the normal control group (n=12), the model group (n=11), the low dose GBE50 group (n=10), and the high dose GBE50 group (n=12). The aging rat model was intraperitoneally injected with D-galactose to establish the aging model for 42 days. Starting from the 22nd day of modeling, rats in the low dose GBE50 group and the high dose GBE50 group were administered by gastrogavage with 75 mg/kg and 150 mg/kg respectively. The protein contents and mRNA expressions of IL-1beta, IL-6, and TNF-a in the prefrontal cortex and hippocampus of rats were detected by radioimmunoassay and Real-time fluorescence quantitative PCR assay respectively. The ultrastructural changes of glia cells in the hippocampal CA1 region were observed by transmission electron microscope. Results The protein contents and mRNA expressions of IL-1beta and TNF-alpha in the prefrontal cortex and the hippocampus of aging rats obviously increased when compared with the normal control group (P < 0.05, P < 0.01). The content of IL-6 in the hippocampus of aging rats obviously decreased (P < 0.01). Compared with the model group, the protein content and mRNA expression of IL-1beta in the prefrontal cortex and the hippocampus were obviously downregulated in the low and high dose GBE50 groups. The content of TNF-alpha in the prefrontal cortex was obviously downregulated in the low and high dose GBE50 groups, the content of TNF-alpha in the hippocampus was obviously downregulated in the low dose GBE50 group (P < 0.05, P < 0.01). The content of IL-6 in the prefrontal cortex of the low dose GBE50 group was up-regulated. The content of IL-6 in the hippocampus of the high dose GBE50 group was also upregulated. The mRNA expression of IL-6 in the prefrontal cortex of the low and high dose GBE50 groups obviously increased (P < 0.05, P < 0.01). Low and high dose GBE50 showed obvious recovery on the ultrastructural damage of glia cells in the hippocampal CA1 region.

CONCLUSIONSGBE50 showed inhibitive effects on the inflammatory reaction of nerves of aging rats. Its mechanism might be possibly correlated with its regulatory effects on the cytokines in the prefrontal cortex and the hippocampus, as well as the ultrastructures of glia cells in the prefrontal cortex and hippocampus to some degree.

Aging ; Animals ; Cytokines ; metabolism ; Ginkgo biloba ; Hippocampus ; cytology ; drug effects ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Male ; Neuroglia ; ultrastructure ; Plant Extracts ; pharmacology ; Prefrontal Cortex ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism