Impaired social behaviour and molecular mediators of associated neural circuits during chronicToxoplasma gondiiinfection in female mice

AbstractToxoplasma gondii(T. gondii) is a neurotropic parasite that is associated with various neuropsychiatric disorders. Rodents infected withT. gondiidisplay a plethora of behavioural alterations, andToxoplasmainfection in humans has been strongly associated with disorders such as schizophrenia, in which impaired social behaviour is an important feature. Elucidating changes at the cellular level relevant to neuropsychiatric conditions can lead to effective therapies. Here, we compare changes in behaviour during an acute and chronicT. gondiiinfection in female mice. Further, we notice that during chronic phase of infection, mice display impaired sociability when exposed to a novel conspecific. Also, we show thatT. gondiiinfected mice display impaired short-term social recognition memory. However, object recognition memory remains intact. Using c-Fos as a marker of neuronal activity, we show that infection leads to an impairment in neuronal activation in the medial prefrontal cortex, hippocampus as well as the amygdala when mice are exposed to a social environment and a change in functional connectivity between these regions. We found changes in synaptic proteins that play a role in the process of neuronal activation such as synaptophysin, PSD-95 and changes in downstream substrates of cell activity such as cyclic AMP, phospho-CREB and BDNF. Our results point towards an imbalance in neuronal activity that can lead to a wider range of neuropsychiatric problems uponT. gondiiinfection.

Download Full-text

Different cholinergic cell groups in the basal forebrain regulate social interaction and social recognition memory

Scientific Reports ◽

10.1038/s41598-021-93045-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kana Okada ◽

Kayo Nishizawa ◽

Tomoko Kobayashi ◽

Shogo Sakata ◽

Kouichi Hashimoto ◽

...

Keyword(s):

Social Interaction ◽

Recognition Memory ◽

Basal Forebrain ◽

Social Behaviour ◽

Cholinergic Neurons ◽

Social Recognition ◽

Social Ability ◽

Cell Groups ◽

Cholinergic Cell ◽

Social Recognition Memory

AbstractSocial behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer’s disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.

Download Full-text

Different cholinergic cell groups in the basal forebrain regulate social interaction and social recognition memory

10.21203/rs.3.rs-119127/v1 ◽

2020 ◽

Author(s):

Kana Okada ◽

Kayo Nishizawa ◽

Tomoko Kobayashi ◽

Shogo Sakata ◽

Kouichi Hashimoto ◽

...

Keyword(s):

Social Interaction ◽

Recognition Memory ◽

Basal Forebrain ◽

Social Behaviour ◽

Cholinergic Neurons ◽

Social Recognition ◽

Social Ability ◽

Cell Groups ◽

Cholinergic Cell ◽

Social Recognition Memory

Abstract Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer’s disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.

Download Full-text

Memory-specific correlated neuronal activity in higher-order auditory regions of a parrot

Scientific Reports ◽

10.1038/s41598-020-80726-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryohei Satoh ◽

Hiroko Eda-Fujiwara ◽

Aiko Watanabe ◽

Yasuharu Okamoto ◽

Takenori Miyamoto ◽

...

Keyword(s):

Neuronal Activity ◽

Higher Order ◽

Auditory Memory ◽

Neuronal Activation ◽

Contact Calls ◽

Contrast Exposure ◽

Auditory Region ◽

Neuronal Representation ◽

Specific Association ◽

Positive Correlations

AbstractMale budgerigars (Melopsittacus undulatus) are open-ended learners that can learn to produce new vocalisations as adults. We investigated neuronal activation in male budgerigars using the expression of the protein products of the immediate early genes zenk and c-fos in response to exposure to conspecific contact calls (CCs: that of the mate or an unfamiliar female) in three subregions (CMM, dNCM and vNCM) of the caudomedial pallium, a higher order auditory region. Significant positive correlations of Zenk expression were found between these subregions after exposure to mate CCs. In contrast, exposure to CCs of unfamiliar females produced no such correlations. These results suggest the presence of a CC-specific association among the subregions involved in auditory memory. The caudomedial pallium of the male budgerigar may have functional subdivisions that cooperate in the neuronal representation of auditory memory.

Download Full-text

Cellular sources of TSPO expression in healthy and diseased brain

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05166-2 ◽

2021 ◽

Author(s):

Erik Nutma ◽

Kelly Ceyzériat ◽

Sandra Amor ◽

Stergios Tsartsalis ◽

Philippe Millet ◽

...

Keyword(s):

Cell Activity ◽

Brain Regions ◽

Cellular Level ◽

Translocator Protein ◽

Disease Stage ◽

Animal Models Of Disease ◽

Positron Emission ◽

Neuropsychiatric Diseases ◽

Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

Download Full-text

Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine

Biomolecules ◽

10.3390/biom11040555 ◽

2021 ◽

Vol 11 (4) ◽

pp. 555

Author(s):

Barbara Rani ◽

Bruna Silva-Marques ◽

Rob Leurs ◽

Maria Beatrice Passani ◽

Patrizio Blandina ◽

...

Keyword(s):

Recognition Memory ◽

Histamine Release ◽

Histidine Decarboxylase ◽

Acetylcholinesterase Inhibitor ◽

Social Recognition ◽

Amnesic Effect ◽

Brain Histamine ◽

Monogamous Species ◽

Social Recognition Memory

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H3R agonist (VUF16839) impaired both STM and LTM. H3R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H3R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H3R stimulation are probably related to their function as heteroreceptors on cholinergic neurons.

Download Full-text

Brain regions activated during consolidation of social recognition memory

Neuroscience Research ◽

10.1016/j.neures.2010.07.1294 ◽

2010 ◽

Vol 68 ◽

pp. e291

Author(s):

Toshiyuki Tanimizu ◽

Kazune Kadoma ◽

Yue Zhang ◽

Hotaka Fukushima ◽

Satoshi Kida

Keyword(s):

Recognition Memory ◽

Brain Regions ◽

Social Recognition ◽

Social Recognition Memory

Download Full-text

Activation of Norepinephrine Neurons in the NTS (A2 population) is Sufficient to Suppress Pulsatile LH Secretion in Female Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1081 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A531-A531

Author(s):

Richard B McCosh ◽

Michael J Kreisman ◽

Katherine Tian ◽

Steven A Thomas ◽

Kellie M Breen

Keyword(s):

Acute Stress ◽

Cell Activity ◽

Metabolic Stress ◽

Pulse Frequency ◽

Designer Drugs ◽

Transduction Efficiency ◽

Neural Pathways ◽

Wild Type ◽

Female Mice ◽

Lh Secretion

Abstract The overarching goal of this work is to identify neural pathways underlying inhibition of pulsatile luteinizing hormone (LH) secretion during stress. Stress-induced suppression of LH secretion is mediated, at least in part, by suppression of arcuate kisspeptin (ARCKiss1) neurons. The mechanisms by which acute stress suppresses ARCKiss1 cell activity are largely unknown; however, several lines of evidence support the hypothesis that A2 neurons (norepinephrine [NE] neurons in the nucleus of the solitary tract [NTS] of the brainstem) are involved. First, A2 cells are activated during several reactive stress paradigms. Second, NE administered into the paraventricular nucleus, which is innervated by A2 neurons, suppressed pulsatile LH secretion. Finally, ablation of brainstem NE neurons restored estrous cyclicity following chronic glucoprivation (chronic metabolic stress model). The present study employed chemogenetics to test the hypothesis that A2 neurons are sufficient to suppress pulsatile LH secretion in ovariectomized female dopamine beta-hydroxylase (DBH) Cre positive and negative (wild type) mice. Mice received bilateral injections of either a Cre-dependent stimulatory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) virus (AAV1-DIO-hM3Dq-mCherry) or a control virus (AAV1-DIO-mCherry) into the NTS. Mice were randomly assigned to receive either clozapine N-oxide (CNO, specific DREADD agonist; 1mg/kg, i.p.) or saline and blood samples were collected at 6-min intervals for 60 min before and 90 min after injection. Two weeks later, mice received the alternate treatment in a cross-over design (n= 5-10/grp). During the pre-injection period, all mice had clear LH pulses (mean: 6.0 ± 0.2 ng/mL, pulses/60 min: 3.4 ± 1.5). In DBH Cre- (wild type) mice with hM3D virus and DBH Cre+ with mCherry virus (both control groups), neither CNO nor saline altered mean LH or LH pulse frequency. However, DBH Cre+ mice with hM3D virus had a 54% reduction in mean LH (p < 0.05) and 59% reduction in pulse frequency (p < 0.05) following CNO; neither LH metric was altered in response to saline. To assess transduction efficiency, fixed neural tissue was collected. In tissue analyzed thus far, DBH Cre+ mice have mCherry labeling in ~70% of DBH-immunoreactive neurons in the NTS and >90% of mCherry neurons contained DBH immunoreactivity. Three DBH Cre+ mice with hM3D virus mice had no LH response to CNO and may represent missed viral injections, which will be determined when tissue is analyzed. These data demonstrate that activation of A2 neurons is sufficient to impair pulsatile LH secretion in female mice. Moreover, these data support the broad hypothesis that the A2 population of neurons is critical for modulating neuroendocrine function during stress and raises the possibility that A2 neurons directly or indirectly influence ARCKiss1 cell activity.

Download Full-text

Social recognition memory: Influence of age, sex, and ovarian hormonal status

Physiology & Behavior ◽

10.1016/j.physbeh.2007.06.020 ◽

2007 ◽

Vol 92 (5) ◽

pp. 881-888 ◽

Cited By ~ 40

Author(s):

Julie A. Markham ◽

Janice M. Juraska

Keyword(s):

Recognition Memory ◽

Social Recognition ◽

Hormonal Status ◽

Social Recognition Memory

Download Full-text

Responses of medullary raphespinal neurons to electrical stimulation of thoracic sympathetic afferents, vagal afferents, and to other sensory inputs in cats

Journal of Neurophysiology ◽

10.1152/jn.1991.66.6.2084 ◽

1991 ◽

Vol 66 (6) ◽

pp. 2084-2094 ◽

Cited By ~ 24

Author(s):

R. W. Blair ◽

A. R. Evans

Keyword(s):

Electrical Stimulation ◽

Neuronal Activity ◽

Vagal Stimulation ◽

Discharge Rate ◽

Stellate Ganglion ◽

Cell Activity ◽

Conditioning Stimulus ◽

Vagal Afferents ◽

Early Peak ◽

Stimulation Of

1. Medullary raphespinal neurons antidromically activated from the T2-T5 segments were tested for responses to electrical stimulation of cervical vagal and thoracic sympathetic afferents (by stimulating the left stellate ganglion), somatic probing, auditory stimuli, and visual stimuli in cats anesthetized with alpha-chloralose. A total of 99 neurons in the raphe nuclei were studied; the locations of 76 cells were histologically confirmed. Neurons were located in raphe magnus (RM, 65%), raphe obscurus (RO, 32%), and raphe pallidus (RPa, 4%). The mean conduction velocity of these neurons was 62 +/- 2.9 (SE) m/s with a range of 1.1-121 m/s. 2. A total of 60/99 tested neurons responded to electrical stimulation of sympathetic afferents. Quantitation of responses was obtained for 55 neurons. With one exception, all responsive neurons were excited and exhibited an early burst of spikes with a mean latency of 16 +/- 1.2 ms. From a spontaneous discharge rate of 5.2 +/- 1.2 spikes/s, neuronal activity increased by 2.9 +/- 0.3 spikes/stimulus. In addition to an early peak, 15 neurons (25%) exhibited a late burst of spikes with a latency of 182 +/- 12.9 ms; neuronal activity increased by 5.0 +/- 1.3 spikes/stimulus. Duration of the late peak (130 +/- 18.5 ms) was longer than for the early peak (18 +/- 0.7 ms), but threshold voltages for eliciting each peak were comparable. Sixteen of 29 spontaneously active neurons exhibited a postexcitatory depression of activity that lasted for 163 +/- 19.1 ms. All but one tested neuron in RO responded to stimulation of sympathetic afferents, but 65% of neurons in RM responded to this stimulus. 3. In response to vagal afferent stimulation, 19% of 57 neurons exhibited inhibition only, 11% were only excited, and 9% were either excited or inhibited, depending on the stimulus paradigm used; the remaining 61% of neurons were unresponsive. From a spontaneous rate of 7.9 +/- 3.8 spikes/s, excited cells increased their discharge rate by 1.6 +/- 0.3 spikes/stimulus. Activity of inhibited cells was reduced from 21.3 +/- 5.8 to 7.8 +/- 3.1 spikes/s. The conditioning-test (CT) technique was used to assess 11 neurons' responses. Stellate ganglion stimulation was the test stimulus, and vagal stimulation the conditioning stimulus. Vagal stimulation reduced the neuronal responses to stellate ganglion stimulation by an average of 50% with a CT interval of 60-100 ms, and cell responses returned to control after 300 ms. With spontaneous cell activity, low frequencies of vagal stimulation were generally excitatory, and high frequencies (10-20 Hz) inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)

Download Full-text