Olfactory bulb is a critical component in encoding and processing olfactory signals, characterized by its intricate neural projections and networks dedicated to this function. It has been found that descending neural projections from the olfactory cortex and other advanced brain regions can modulate the excitability of olfactory bulb output neurons in the olfactory bulb, either directly or indirectly, which can further influence olfactory discrimination, learning, and other abilities. In recent years, advancements in optogenetic technology have facilitated extensive application of neuron manipulation for studying neural circuits, thereby greatly accelerating research into olfactory mechanisms. This review summarizes the latest research progress on the regulatory effects of neural projections from the olfactory cortex, basal forebrain, raphe nucleus, and locus coeruleus on olfactory bulb function. Furthermore, the important role that photogenetic technology plays in olfactory mechanism research is evaluated. Finally, the existing problems and future development trends in current research are preliminarily proposed and explained. This review aims to provide new insights into the mechanisms underlying olfactory neural regulation as well as applications of optogenetic technology, which are crucial for advancing the research on olfactory mechanism and the application of optogenetic technology.
Olfactory Bulb/physiology* ; Optogenetics/methods* ; Animals ; Humans ; Olfactory Pathways/physiology* ; Olfactory Cortex/physiology* ; Smell/physiology*

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Depressive Disorder, Major/metabolism* ; Basal Forebrain ; Depression ; Hippocampus/metabolism* ; Cholinergic Agents

Basal Forebrain ; Cholinergic Agents ; Cholinergic Neurons ; Humans ; Receptors, Histamine H1 ; Schizophrenia

Entorhinal Cortex/physiology* ; Hippocampus/physiology* ; Neural Pathways/physiology*

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (I_h), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the I_h. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
Animals ; Chronic Pain ; Entorhinal Cortex/metabolism* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Neurons/metabolism* ; Rats ; Receptors, Dopamine D1/metabolism* ; Receptors, Dopamine D2

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

The method of directly using speed information and angle information to drive attractors model of grid cells to encode environment has poor anti-interference ability and is not bionic. In response to the problem, this paper proposes a grid field calculation model based on perceived speed and perceived angle. The model has the following characteristics. Firstly, visual stream is decoded to obtain visual speed, and speed cell is modeled and decoded to obtain body speed. Visual speed and body speed are integrated to obtain perceived speed information. Secondly, a one-dimensional circularly connected cell model with excitatory connection is used to simulate the firing mechanism of head direction cells, so that the robot obtains current perception angle information in a biomimetic manner. Finally, the two kinds of perceptual information of speed and angle are combined to realize the driving of grid cell attractors model. The proposed model was experimentally verified. The results showed that this model could realize periodic hexagonal firing field mode of grid cells and precise path integration function. The proposed algorithm may provide a foundation for the research on construction method of robot cognitive map based on hippocampal cognition mechanism.
Action Potentials ; Computer Simulation ; Computer Systems ; Entorhinal Cortex ; Grid Cells ; Hippocampus ; Models, Neurological

The basolateral amygdala (BLA) receives dense projections from cholinergic neurons of the basal forebrain. Acetylcholine can contributes to amygdala-dependent behaviors: formation and extinction of fear memory and appetitive instrumental learning. However, the cholinergic mechanism at the circuit level has not been defined yet. We demonstrated that cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons exhibits a retrograde form of short-term synaptic inhibition, depolarization-induced suppression of inhibition (DSI). Activation of nicotinic receptors was sufficient to evoke action potentials in cholecystokinin (CCK)-positive inhibitory neurons, which strongly inhibit pyramidal neurons through their perisomatic synapses. Our cell type-specific monosynaptic retrograde tracing also revealed that CCK neurons are innervated by basal forebrain cholinergic neurons. Therefore, our data indicated that CCK inhibitory neurons mediate the cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons.
Acetylcholine ; Action Potentials ; Basal Forebrain ; Basolateral Nuclear Complex ; Cholecystokinin ; Cholinergic Neurons ; Conditioning, Operant ; Iontophoresis ; Memory ; Neurons ; Pyramidal Cells ; Receptors, Nicotinic ; Synapses

The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.
Action Potentials ; drug effects ; Animals ; Basal Forebrain ; cytology ; Dimaprit ; pharmacology ; Dose-Response Relationship, Drug ; Electric Stimulation ; Female ; GABAergic Neurons ; drug effects ; Histamine ; pharmacology ; Histamine Agonists ; pharmacology ; Lysine ; analogs & derivatives ; metabolism ; Male ; Patch-Clamp Techniques ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; metabolism ; Receptors, Histamine H2 ; metabolism ; Sodium Channel Blockers ; pharmacology ; Tetrodotoxin ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.
CA3 Region, Hippocampal ; physiopathology ; Electroencephalography ; Entorhinal Cortex ; physiopathology ; Epilepsy, Temporal Lobe ; physiopathology ; Humans ; Male ; Theta Rhythm