Prefrontal and lateral entorhinal neurons co-dependently learn item-outcome rules.

The ability to learn novel items depends on brain functions that store information about items classified by their associated meanings and outcomes, but the underlying neural circuit mechanisms of this process remain poorly understood. Here we show that deep layers of the lateral entorhinal cortex (LEC) contain two groups of 'item-outcome neurons': one developing activity for rewarded items during learning, and another for punished items. As mice learned an olfactory item-outcome association, we found that the neuronal population of LEC layers 5/6 (LEC) formed an internal map of pre-learned and novel items, classified into dichotomic rewarded versus punished groups.

Circuit dynamics of the olfactory pathway during olfactory learning.

The olfactory system plays crucial roles in perceiving and interacting with their surroundings. Previous studies have deciphered basic odor perceptions, but how information processing in the olfactory system is associated with learning and memory is poorly understood. In this review, we summarize recent studies on the anatomy and functional dynamics of the mouse olfactory learning pathway, focusing on how neuronal circuits in the olfactory bulb (OB) and olfactory cortical areas integrate odor information in learning.

Biologically plausible local synaptic learning rules robustly implement deep supervised learning.

In deep neural networks, representational learning in the middle layer is essential for achieving efficient learning. However, the currently prevailing backpropagation learning rules (BP) are not necessarily biologically plausible and cannot be implemented in the brain in their current form. Therefore, to elucidate the learning rules used by the brain, it is critical to establish biologically plausible learning rules for practical memory tasks.

Entorhinal cortex dysfunction in Alzheimer's disease.

The entorhinal cortex (EC) is the brain region that often exhibits the earliest histological alterations in Alzheimer's disease (AD), including the formation of neurofibrillary tangles and cell death. Recently, brain imaging studies from preclinical AD patients and electrophysiological recordings from AD animal models have shown that impaired neuronal activity in the EC precedes neurodegeneration. This implies that memory impairments and spatial navigation deficits at the initial stage of AD are likely caused by activity dysfunction rather than by cell death.

Reconciling neuronal representations of schema, abstract task structure, and categorization under cognitive maps in the entorhinal-hippocampal-frontal circuits.

Learning leads to a neuronal representation of acquired knowledge. This idea of knowledge representation was traditionally developed as a "cognitive map" of spatial memory represented in the hippocampus. The framework of cognitive mapping has been extended in the past decade to include not only spatial memory, but also non-spatial factual and temporal memory.

Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer's disease.

Clinical evidence suggests that the entorhinal cortex is a primary brain area triggering memory impairments in Alzheimer's disease (AD), but the underlying brain circuit mechanisms remain largely unclear. In healthy brains, sharp-wave ripples (SWRs) in the hippocampus and entorhinal cortex play a critical role in memory consolidation. We tested SWRs in the MEC layers 2/3 of awake amyloid precursor protein knock-in (APP-KI) mice, recorded simultaneously with SWRs in the hippocampal CA1.

Dopamine facilitates associative memory encoding in the entorhinal cortex.

Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning. However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory. Here, using cell-type-specific electrophysiological recording, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC).

Protocol for remapping of place cells in disease mouse models.

Hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments called "remapping," and we have recently shown that remapping of place cells becomes disrupted in a mouse model of Alzheimer's disease. Here, we describe our protocol for investigating remapping of place cells and grid cells using a custom-made electrophysiology device, with detailed descriptions and problem-solving tips for the construction and implantation of the recording device. We also provide steps for behavioral training, recording, and data analysis.

Disrupted Place Cell Remapping and Impaired Grid Cells in a Knockin Model of Alzheimer's Disease.

Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called "remapping." We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory.

Parallel odor processing by mitral and middle tufted cells in the olfactory bulb.

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations.

Gamma oscillations in the entorhinal-hippocampal circuit underlying memory and dementia.

Gamma oscillations that occur within the entorhinal cortex-hippocampal circuitry play important roles in the formation and retrieval of memory in healthy brains. Recent studies report that gamma oscillations are impaired in the entorhinal-hippocampal circuit of Alzheimer's disease (AD) patients and AD animal models. Here we review the latest advancements in studies of entorhinal-hippocampal gamma oscillations in healthy memory and dementia.

Impaired Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30-100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus.

Functional optical coherence tomography of rat olfactory bulb with periodic odor stimulation.

In rodent olfactory bulb (OB), optical intrinsic signal imaging (OISI) is commonly used to investigate functional maps to odorant stimulations. However, in such studies, the spatial resolution in depth direction (z-axis) is lost because of the integration of light from different depths. To solve this problem, we propose functional optical coherence tomography (fOCT) with periodic stimulation and continuous recording.

The entorhinal map of space.

How do we know where we are, and how do we remember the places we visited? Since the discovery of place cells in 1971, our understanding of the brain's maps of external space has exploded. Yet the origin of the place-cell signal remained elusive. The discovery of grid cells in the medial entorhinal cortex (MEC) in 2005 put place cells in a context, since the existence of grid cells pointed to circuit mechanisms that might explain the formation of place cells.

Plasticity in oscillatory coupling between hippocampus and cortex.

Neural oscillations observed in local field potentials (LFP) represent gross cellular activity near the recording electrode. Coupling of oscillations in distributed brain circuits has been proposed to enhance communication across the circuits, and the plasticity in oscillatory coupling can underlie flexible task learning, but the direct evidence has been lacking. Recently, evidence for plasticity in oscillatory coupling in theta, beta and gamma bands has been obtained in memory circuits consisted of the hippocampus and its connected areas, suggesting importance of oscillatory coupling plasticity in memory processing.

Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus.

We asked whether the structural heterogeneity of the hippocampal CA3-CA2 axis is reflected in how space is mapped onto place cells in CA3-CA2. Place fields were smaller and sharper in proximal CA3 than in distal CA3 and CA2. The proximodistal shift was accompanied by a progressive loss in the ability of place cells to distinguish configurations of the same spatial environment, as well as a reduction in the extent to which place cells formed uncorrelated representations for different environments.

Functional diversity along the transverse axis of hippocampal area CA1.

Decades of neuroscience research have shed light on the hippocampus as a key structure for the formation of episodic memory. The hippocampus is divided into distinct subfields - CA1, CA2 and CA3. While accumulating evidence points to cellular and synaptic heterogeneity within each subfield, this heterogeneity has not received much attention in computational and behavioural studies and subfields have until recently been considered functionally uniform.

Coordination of entorhinal-hippocampal ensemble activity during associative learning.

Accumulating evidence points to cortical oscillations as a mechanism for mediating interactions among functionally specialized neurons in distributed brain circuits. A brain function that may use such interactions is declarative memory--that is, memory that can be consciously recalled, such as episodes and facts. Declarative memory is enabled by circuits in the entorhinal cortex that interface the hippocampus with the neocortex.

Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex.

Odor signals are conveyed from the olfactory bulb to the olfactory cortex (OC) by mitral cells (MCs) and tufted cells (TCs). However, whether and how the two types of projection neuron differ in function and axonal connectivity is still poorly understood. Odor responses and axonal projection patterns were compared between MCs and TCs in mice by visualizing axons of electrophysiologically identified single neurons.

Genetic visualization of the secondary olfactory pathway in Tbx21 transgenic mice.

Background: Mitral and tufted cells are the projection neurons in the olfactory bulb, conveying odour information to various regions of the olfactory cortex. In spite of their functional importance, there are few molecular and genetic tools that can be used for selective labelling or manipulation of mitral and tufted cells. Tbx21 was first identified as a T-box family transcription factor regulating the differentiation and function of T lymphocytes.

Swept source optical coherence tomography as a tool for real time visualization and localization of electrodes used in electrophysiological studies of brain in vivo.

In studies of in vivo extracellular recording, we usually penetrate electrodes almost blindly into the neural tissue, in order to detect the neural activity from an expected target location at a certain depth. After the recording, it is necessary for us to determine the position of the electrodes precisely. Generally, to identify the position of the electrode, one method is to examine the postmortem tissue sample at micron resolution.

In vivo layer visualization of rat olfactory bulb by a swept source optical coherence tomography and its confirmation through electrocoagulation and anatomy.

Here, we report in vivo 3-D visualization of the layered organization of a rat olfactory bulb (OB) by a swept source optical coherence tomography (SS-OCT). The SS-OCT operates at a wavelength of 1334 nm with respective theoretical depth and lateral resolutions of 6.7 μm and 15.

Two highly homologous mouse odorant receptors encoded by tandemly-linked MOR29A and MOR29B genes respond differently to phenyl ethers.

Since the discovery of odorant receptors (ORs) in rodents, most ORs have remained orphan receptors. Even for deorphanized ORs in vitro, their in vivo properties are largely unknown. Here, we report odor response profiles of two highly homologous mouse ORs, MOR29A and MOR29B, both in vivo and in vitro.

Differential axonal projection of mitral and tufted cells in the mouse main olfactory system.

In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB) glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy.