Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation.

Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses.

Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.

The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found.

Synaptic Engram.

The concept of the engram refers to structural and/or physiological changes that underlie memory associations during learning. However, the precise biological basis of the engram remains elusive, with ongoing controversy regarding whether it resides at the cellular level or within the synaptic connections between activated cells. Here, we briefly review the studies investigating the cellular engram and the challenges they encounter.

Synaptic correlates of the corticocortical circuit in motor learning.

Rodents actively learn new motor skills for survival in reaction to changing environments. Despite the classic view of the primary motor cortex (M1) as a simple muscle relay region, it is now known to play a significant role in motor skill acquisition. The secondary motor cortex (M2) is reported to be a crucial region for motor learning as well as for its role in motor execution and planning.

Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain.

Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling.

Memory allocation at the neuronal and synaptic levels.

Memory allocation, which determines where memories are stored in specific neurons or synapses, has consistently been demonstrated to occur via specific mechanisms. Neuronal allocation studies have focused on the activated population of neurons and have shown that increased excitability via cAMP response element-binding protein (CREB) induces a bias toward memoryencoding neurons. Synaptic allocation suggests that synaptic tagging enables memory to be mediated through different synaptic strengthening mechanisms, even within a single neuron.

Activated somatostatin interneurons orchestrate memory microcircuits.

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA).

Plasticity of Dendritic Spines Underlies Fear Memory.

The brain has the powerful ability to transform experiences into anatomic maps and continuously integrate massive amounts of information to form new memories. The manner in which the brain performs these processes has been investigated extensively for decades. Emerging reports suggest that dendritic spines are the structural basis of information storage.

Ubiquitination of the GluA1 Subunit of AMPA Receptors Is Required for Synaptic Plasticity, Memory, and Cognitive Flexibility.

Activity-dependent changes in the number of AMPA-type glutamate receptors (AMPARs) at the synapse underpin the expression of LTP and LTD, cellular correlates of learning and memory. Post-translational ubiquitination has emerged as a key regulator of the trafficking and surface expression of AMPARs, with ubiquitination of the GluA1 subunit at Lys-868 controlling the post-endocytic sorting of the receptors into the late endosome for degradation, thereby regulating their stability at synapses. However, the physiological significance of GluA1 ubiquitination remains unknown.

Loosely synchronized activation of anterior cingulate cortical neurons for scratching response during histamine-induced itch.

Itch is a distinctive sensation that causes a specific affection and scratching reaction. The anterior cingulate cortex (ACC) has been linked to itch sensation in numerous studies; however, its precise function in processing pruritic inputs remains unknown. Distinguishing the precise role of the ACC in itch sensation can be challenging because of its capacity to conduct heterologous neurophysiological activities.

How engram mediates learning, extinction, and relapse.

Fear learning ensures survival through an expression of certain behavior as a conditioned fear response. Fear memory is processed and stored in a fear memory circuit, including the amygdala, hippocampus, and prefrontal cortex. A gradual decrease in conditioned fear response can be induced by fear extinction, which is mediated through the weakening of the original fear memory traces and the newly formed inhibition of those traces.

Cyclic AMP response element-binding protein (CREB) transcription factor in astrocytic synaptic communication.

Astrocytes are known to actively participate in synaptic communication by forming structures called tripartite synapses. These synapses consist of presynaptic axon terminals, postsynaptic dendritic spines, and astrocytic processes where astrocytes release and receive transmitters. Although the transcription factor cyclic AMP response element (CRE)-binding protein (CREB) has been actively studied as an important factor for mediating synaptic activity-induced responses in neurons, its role in astrocytes is relatively unknown.

Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo.

As basic units of neural networks, ensembles of synapses underlie cognitive functions such as learning and memory. These synaptic engrams show elevated synaptic density among engram cells following contextual fear memory formation. Subsequent analysis of the CA3-CA1 engram synapse revealed larger spine sizes, as the synaptic connectivity correlated with the memory strength.

Synaptic ensembles between raphe and DR-containing accumbens shell neurons underlie postisolation sociability in males.

Social animals expend considerable energy to maintain social bonds throughout their life. Male and female mice show sexually dimorphic behaviors, yet the underlying neural mechanisms of sociability and their dysregulation during social disconnection remain unknown. Dopaminergic neurons in dorsal raphe nucleus (DRN) is known to contribute to a loneliness-like state and modulate sociability.

The Three Musketeers in the Medial Prefrontal Cortex: Subregion-specific Structural and Functional Plasticity Underlying Fear Memory Stages.

Fear memory recruits various brain regions with long-lasting brain-wide subcellular events. The medial prefrontal cortex processes the emotional and cognitive functions required for adequately handling fear memory. Several studies have indicated that subdivisions within the medial prefrontal cortex, namely the prelimbic, infralimbic, and anterior cingulate cortices, may play different roles across fear memory states.

Distinct cell populations of ventral tegmental area process motivated behavior.

It is well known that dopamine transmission from the ventral tegmental area (VTA) modulates motivated behavior and reinforcement learning. Although dopaminergic neurons are the major type of VTA neurons, recent studies show that a significant proportion of the VTA contains GABAergic and type 2 vesicular glutamate transporter (VGLUT2)-positive neurons. The non-dopaminergic neurons are also critically involved in regulating motivated behaviors.

The complexity of ventral CA1 and its multiple functionalities.

The hippocampus is one of the most widely investigated brain regions with its massive contributions to multiple behaviours. Especially, the hippocampus is subdivided into the dorsal and ventral parts playing distinct roles. In this review, we will focus on the ventral hippocampus, especially the ventral CA1 (vCA1), whose role is being actively discovered.

Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD.

In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown.

Interrogating structural plasticity among synaptic engrams.

Our daily experiences and learnings are stored in the form of memories. These experiences trigger synaptic plasticity and persistent structural and functional changes in neuronal synapses. Recently, cellular studies of memory storage and engrams have emerged over the last decade.