The small conductance Ca-activated K channel activator GW542573X impairs hippocampal memory in C57BL/6J mice.

Small conductance Ca-activated K (SK) channels, expressed throughout the CNS, are comprised of SK1, SK2 and SK3 subunits, assembled as homotetrameric or heterotetrameric proteins. SK channels expressed somatically modulate the excitability of neurons by mediating the medium component of the afterhyperpolarization. Synaptic SK channels shape excitatory postsynaptic potentials and synaptic plasticity.

Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice.

A central question in the field of aging research is to identify the cellular and molecular basis of neuroresilience. One potential candidate is the small GTPase, Rab10. Here, we used Rab10 mice to investigate the molecular mechanisms underlying Rab10-mediated neuroresilience.

DREADD-inactivation of dorsal CA1 pyramidal neurons in mice impairs retrieval of object and spatial memories.

The hippocampus, a medial temporal lobe brain region, is critical for the consolidation of information from short-term memory into long-term episodic memory and for spatial memory that enables navigation. Hippocampal damage in humans has been linked to amnesia and memory loss, characteristic of Alzheimer's disease and other dementias. Numerous studies indicate that the rodent hippocampus contributes significantly to long-term memory for spatial and nonspatial information.

Mice recognize 3D objects from recalled 2D pictures, support for picture-object equivalence.

Picture-object equivalence or recognizing a three-dimensional (3D) object after viewing a two-dimensional (2D) photograph of that object, is a higher-order form of visual cognition that may be beyond the perceptual ability of rodents. Behavioral and neurobiological mechanisms supporting picture-object equivalence are not well understood. We used a modified visual recognition memory task, reminiscent of those used for primates, to test whether picture-object equivalence extends to mice.

Object Recognition Memory: Distinct Yet Complementary Roles of the Mouse CA1 and Perirhinal Cortex.

While the essential contribution of the hippocampus to spatial memory is well established, object recognition memory has been traditionally attributed to the perirhinal cortex (PRh). However, the results of several studies indicate that under specific procedural conditions, temporary or permanent lesions of the hippocampus affect object memory processes as measured in the Spontaneous Object Recognition (SOR) task. The PRh and hippocampus are considered to contribute distinctly to object recognition memory based on memory strength.

ADAP1/Centaurin-α1 Negatively Regulates Dendritic Spine Function and Memory Formation in the Hippocampus.

ADAP1/Centaurin-α1 (CentA1) functions as an Arf6 GTPase-activating protein highly enriched in the brain. Previous studies demonstrated the involvement of CentA1 in brain function as a regulator of dendritic differentiation and a potential mediator of Alzheimer's disease (AD) pathogenesis. To better understand the neurobiological functions of CentA1 signaling in the brain, we developed knock-out (KO) mice.

Object and place information processing by CA1 hippocampal neurons of C57BL/6J mice.

Medial and lateral entorhinal cortices convey spatial/contextual and item/object information to the hippocampus, respectively. Whether the distinct inputs are integrated as one cognitive map by hippocampal neurons to represent location and the objects therein, or whether they remain as parallel outputs, to be integrated in a downstream region, remains unclear. Principal, or complex spike bursting, neurons of hippocampus exhibit location-specific firing, and it is likely that the activity of "place cells" supports spatial memory/navigation in rodents.

Small-Conductance Ca-Activated K Channel 2 in the Dorsal Horn of Spinal Cord Participates in Visceral Hypersensitivity in Rats.

Visceral hypersensitivity is a highly complex and subjective phenomenon associated with multiple levels of the nervous system and a wide range of neurotransmission. The dorsal horn (DH) in spinal cord relays the peripheral sensory information into the brain. Small conductance Ca-activated K (SK) channels regulate neuronal excitability and firing by allowing K to efflux in response to increase in the intracellular Ca level.

Encoding of contextual fear memory requires proteins in the prelimbic cortex.

Background: Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory.

Methods: Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse.

Effect of a hallucinogenic serotonin 5-HT receptor agonist on visually guided, hippocampal-dependent spatial cognition in C57BL/6J mice.

By acting on serotonin 5-HT receptors (5-HT Rs), serotonergic psychedelic drugs induce perceptual and visual hallucinations by increasing neuronal excitability and altering visual-evoked neuronal responses. The present study was designed to examine whether the perceptual alterations induced by a serotonergic psychedelic drug would affect the integrity of hippocampal-dependent, visually guided spatial cognition. phenylalkylamine hallucinogen TCB-2 is a selective agonist of 5-HT Rs.

Blockade of Serotonin 5-HT Receptors Suppresses Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice.

Unlabelled: The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate - even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal.

Temporary inactivation reveals that the CA1 region of the mouse dorsal hippocampus plays an equivalent role in the retrieval of long-term object memory and spatial memory.

Recognition of a previously experienced item or object depends upon the successful retrieval of memory for the object. The neural mechanisms that support object recognition memory in the mammalian brain are not well understood. The rodent hippocampus plays a well-established role in spatial memory, and we previously demonstrated that temporary inactivation of the mouse hippocampus impairs object memory, as assessed with a novel object preference (NOP) test.

Examination of the hippocampal contribution to serotonin 5-HT2A receptor-mediated facilitation of object memory in C57BL/6J mice.

The rodent hippocampus supports non-spatial object memory. Serotonin 5-HT2A receptors (5-HT2AR) are widely expressed throughout the hippocampus. We previously demonstrated that the activation of 5-HT2ARs enhanced the strength of object memory assessed 24 h after a limited (i.

The role of serotonin 5-HT2A receptors in memory and cognition.

Serotonin 5-HT2A receptors (5-HT2ARs) are widely distributed in the central nervous system, especially in brain region essential for learning and cognition. In addition to endogenous 5-HT, several hallucinogens, antipsychotics, and antidepressants function by targeting 5-HT2ARs. Preclinical studies show that 5-HT2AR antagonists have antipsychotic and antidepressant properties, whereas agonist ligands possess cognition-enhancing and hallucinogenic properties.

Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice.

Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine.

Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization.

Assessing rodent hippocampal involvement in the novel object recognition task. A review.

The novel object recognition (NOR) task has emerged as a popular method for testing the neurobiology of nonspatial memory in rodents. This task exploits the natural tendency of rodents to explore novel items and depending on the amount of time that rodents spend exploring the presented objects, inferences about memory can be established. Despite its wide use, the underlying neural circuitry and mechanisms supporting NOR have not been clearly defined.

The neurosteroid allopregnanolone impairs object memory and contextual fear memory in male C57BL/6J mice.

Allopregnanolone (ALLO, or 3α-hydroxy-5α-pregnan-20-one) is a steroid metabolite of progesterone and a potent endogenous positive allosteric modulator of GABA-A receptors. Systemic ALLO has been reported to impair spatial, but not nonspatial learning in the Morris water maze (MWM) and contextual memory in rodents. These cognitive effects suggest an influence of ALLO on hippocampal-dependent memory, although the specific nature of the neurosteroid's effects on learning, memory or performance is unclear.

The rodent hippocampus is essential for nonspatial object memory.

Elucidating the role of the rodent hippocampus in object recognition memory is critical for establishing the appropriateness of rodents as models of human memory and for their use in the development of memory disorder treatments. In mammals, spatial memory and nonspatial memory depend upon the hippocampus and associated medial temporal lobe (MTL) structures. Although well established in humans, the role of the rodent hippocampus in object memory remains highly debated due to conflicting findings across temporary and permanent hippocampal lesion studies and evidence that the perirhinal cortex may support object memory.

Directional responding of C57BL/6J mice in the Morris water maze is influenced by visual and vestibular cues and is dependent on the anterior thalamic nuclei.

Recent findings indicate that rats navigate in spatial tasks such as the Morris water maze (MWM) using a local cue-based reference frame rather than a distal cue-based reference frame. Specifically, rats swim in a particular direction to a location relative to pool-based cues, rather than to an absolute location defined by room-based cues. Neural mechanisms supporting this bias in rodents for relative responding in spatial tasks are not yet understood.

Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice.

Excessive fear is a hallmark of several emotional and mental disorders such as phobias and panic disorders. Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in an effort to identify mechanisms that may hold clinical significance for remediating aberrant fear memory. Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targets mediating such effects.

The SK2-long isoform directs synaptic localization and function of SK2-containing channels.

SK2-containing channels are expressed in the postsynaptic density (PSD) of dendritic spines on mouse hippocampal area CA1 pyramidal neurons and influence synaptic responses, plasticity and learning. The Sk2 gene (also known as Kcnn2) encodes two isoforms that differ only in the length of their N-terminal domains. SK2-long (SK2-L) and SK2-short (SK2-S) are coexpressed in CA1 pyramidal neurons and likely form heteromeric channels.

In vivo pharmacological manipulation of small conductance Ca(2+)-activated K(+) channels influences motor behavior, object memory and fear conditioning.

Small conductance Ca(2+)-activated K(+) channels (SK, K(Ca2.1), K(Ca2.2), K(Ca2.

Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats.

Background: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders.

Contextual memory deficits observed in mice overexpressing small conductance Ca2+-activated K+ type 2 (KCa2.2, SK2) channels are caused by an encoding deficit.

Hippocampal-dependent synaptic plasticity and memory are modulated by apamin-sensitive small conductance Ca2+-activated K+ (SK) channels. Transgenic mice overexpressing SK2 channels (SK2+/T mice) exhibit marked deficits in hippocampal memory and synaptic plasticity, as previously reported. Here, we examined whether SK2 overexpression affects the encoding or retention of contextual memory.