Hongbo Jia

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences · Brain Research Instrument Innovation Center

In sensory cortex regions, neurons are tuned to specific stimulus features. For example, in the visual cortex, many neurons fire predominantly in response to moving objects of a preferred orientation. However, the characteristics of the synaptic input that cortical neurons receive to generate their output firing pattern remain unclear. Here we repo...

Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains. However, the extent of such studies is typically confined to a single functional region of the brain. Here, we demonstrate a novel technique, termed the multiarea two-photon real-time in v...

The sensory responses of cortical neuronal populations following training have been extensively studied. However, the spike firing properties of individual cortical neurons following training remain unknown. Here, we have combined two-photon Ca2+ imaging and single-cell electrophysiology in awake behaving mice following auditory associative trainin...

Urination, a vital and conserved process of emptying urine from the urinary bladder in mammals, requires precise coordination between the bladder and external urethra sphincter (EUS) that is tightly controlled by a complex neural network. However, the specific subpopulation of neurons that accounts for such coordination remains unidentified, limiti...

Previous studies based on layer specificity suggest that ascending signals from the thalamus to sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mappe...

Previous studies based on layer specificity suggest that ascending signals from the thalamus to sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mappe...

Previous studies based on layer specificity suggest that ascending signals from the thalamus to sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mappe...

Two-photon Ca²⁺ imaging technology increasingly plays an essential role in neuroscience research. However, the requirement for extensive professional annotation poses a significant challenge to improving the performance of neuron segmentation models. Here, we present NeuroSeg-III, an innovative self-supervised learning approach specifically designe...

Stimulating collagen production in skin helps to enhance vitality while decelerating aging- associated processes in skin tissue. However, current approaches to enhancing collagen production are commonly limited by accompanying pain and trauma. Here, we report that mid-infrared modulation (MIMO) at an intensity of 70 mW/cm ² promotes collagen produc...

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca²⁺ imaging and targeted single-cell loose-patch record...

Optical coherence tomography (OCT) technology has significant potential value in the application of early gastrointestinal tumor screening and intraoperative guidance. In the application of diagnosing gastrointestinal diseases, a key step of OCT image intelligent analysis system is to segment the tissues and layers accurately. In this paper, we pro...

Significance: The studying of rapid neuronal signaling across large spatial scales in intact, living brains requires both high temporal resolution and versatility of the measurement device. Aim: We introduce a high-speed two-photon microscope based on a custom-built acousto-optic deflector (AOD). This microscope has a maximum line scan frequency...

The prevalence and disease burden of urolithiasis has increased substantially worldwide in the last decade, and intraluminal holmium laser lithotripsy has become the primary treatment method. However, inappropriate laser energy settings increase the risk of perioperative complications, largely due to the lack of intraoperative information on the st...

The development of two-photon microscopy and Ca2+ indicators has enabled the recording of multiscale neuronal activities in vivo and thus advanced the understanding of brain functions. However, it is challenging to perform automatic, accurate, and generalized neuron segmentation when processing a large amount of imaging data. Here, we propose a nov...

Neocortical layer 6 (L6) is less understood than other more superficial layers, largely owing to limitations of performing high-resolution investigations in vivo. Here, we show that labeling with the Challenge Virus Standard (CVS) rabies virus strain enables high-quality imaging of L6 neurons by conventional two-photon microscopes. CVS virus inject...

The sensory neocortex has been since long suggested to be a substrate for long-term memory storage, yet which exact cells store long-term memories remained neither known nor visible over a century. Here, using a combination of day-by-day two-photon Ca ²⁺ imaging and targeted single-cell loose-patch recording in a non-fear auditory associative learn...

Quantitative and mechanistic understanding of learning and long-term memory at the level of single neurons in living brains require highly demanding techniques. A specific need is to precisely label one cell whose firing output property is pinpointed amidst a functionally characterized large population of neurons through the learning process and th...

The ability to form predictions based on recent sensory experience is essential for behavioral adaptation to our ever-changing environment. Predictive encoding represented by neuronal activity has been observed in sensory cortex, but how this neuronal activity is transformed into anticipatory motor behavior remains unclear. Fiber photometry to inve...

The hippocampal CA2 region plays a key role in social memory. The encoding of such memory involves afferent activity from the hypothalamic supramammillary nucleus (SuM) to CA2. However, the neuronal circuits required for consolidation of freshly encoded social memory remain unknown. Here, we used circuit-specific optical and single-cell electrophys...

Astrocytic Ca2+ transients are essential for astrocyte integration into neural circuits. These Ca2+ transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and...

The olivocerebellar circuitry is important to convey both motor and non-motor information from the inferior olive (IO) to the cerebellar cortex. Several methods are currently established to observe the dynamics of the olivocerebellar circuitry, largely by recording the complex spike activity of cerebellar Purkinje cells; however, these techniques c...

Two-photon Ca2+ imaging is a widely used technique for investigating brain functions across multiple spatial scales. However, the recording of neuronal activities is affected by movement of the brain during tasks in which the animal is behaving normally. Although post-hoc image registration is the commonly used approach, the recent developments of...

Reconstructing axonal projections of single neurons at the whole-brain level is currently a converging goal of the neuroscience community that is fundamental for understanding the logic of information flow in the brain. Thousands of single neurons from different brain regions have recently been morphologically reconstructed, but the corresponding p...

Currently, the most effective strategy for dealing with Alzheimer's disease (AD) is delaying the onset of dementia. Severe hypoglycemia is strongly associated with dementia; however, the effects of recurrent moderate hypoglycemia (RH) on progression of cognitive deficits in diabetic patients with genetic susceptibility to AD remain unclear. Here, w...

Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (MIM), that delivers mid-infrared light energy through the opened skull or...

Two-photon Ca²⁺ imaging is a leading technique for recording neuronal activities in vivo with cellular or subcellular resolution. However, during experiments, the images often suffer from corruption due to complex noises. Therefore, the analysis of Ca²⁺ imaging data requires preprocessing steps, such as denoising, to extract biologically relevant i...

Reconstructing axonal projections of single neurons at whole-brain level is a currently converging goal of the neuroscience community, which is fundamental to understanding the logic of information flow in the brain. Thousands of single neurons from different brain regions recently have been morphologically reconstructed, but the corresponding phys...

Background: Recurrent moderate hypoglycemia (RH), a major adverse effect of hypoglycemic therapy in diabetic patients, is one of the main risk factors for cognitive impairment and dementia. Transient receptor potential canonical channel 6 (TRPC6) is a potential therapeutic target for Alzheimer's disease (AD) and its expression is highly regulated...

Boosting learning capability represents a long-sought dream of mankind. Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (M...

Background To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Method In this multi-c...

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Par...

Two-photon laser scanning microscopy, originally developed since 1990s, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel mult...

Urination (also called micturition) is thought to be regulated by a neural network that is distributed in both subcortical and cortical regions. Previously, urination-related neurons have been identified in subcortical structures such as the pontine micturition center (also known as Barrington’s nucleus). However, the origin of the descending corti...

Video S1. Ca2+ Signals in the MECII-DG Projection of a Freely Exploring Animal in a Novel Chamber, Related to Figure 1 Representative Ca2+ signals in the MECII-DG projection and the corresponding exploratory behavior in a new chamber. The movie plays 5 times faster than the raw movie.

Video S3. Optogenetic Inhibition Experiments during the Morris Water Maze Task, Related to Figure 4 Three consecutive trials (light-off, light-on and light-off) during the water maze task performance are shown for a well-trained mouse.

Video S2. PTA Activity in a Well-Trained Mouse during the Water Maze Task, Related to Figure 1 Representative Ca2+ signals in the MECII-DG projection and the corresponding behavioral task in the water maze. Both the start and the end points of the performance are indicated by vertical blue lines.

The ability to remember and to navigate to safe places is necessary for survival. Place navigation is known to involve medial entorhinal cortex (MEC)-hippocampal connections. However, learning-dependent changes in neuronal activity in the distinct circuits remain unknown. Here, by using optic fiber photometry in freely behaving mice, we discovered...

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral loc...

The procedure of the head-post implantation. (A) Image of an anesthetized mouse on the surgery table in the stereotaxis instrument. (B) Hair removal using hair removal cream. (C) Wash with Betadine to prepare for skin removal. (D) Skin removal and tissue cleaning. (E) Adherence of the head-post.

Comparison of imaging data before and after motion correction. (Left) Video of a mouse performing the sound-triggered licking task. (Middle) Population imaging of L2/3 neurons in Au1 synchronized with the licking behavior of the mouse in the Left. The apparent X-Y axis motion artifacts were presented. (Right) Population imaging data of the Middle a...

The weights (g) of each mouse across training.

3D print file for body tube.

3D print file for recording chamber.

Comparison of the Ca2+ transients before and after image registration. (A) An averaged image (400 frames) from a behaving mouse. (B) The Ca2+ transients of 3 consecutive trials from 3 neurons (outlined in A) before registration. (C) The Ca2+ transients of 3 consecutive trials of 3 neurons (outlined in A) after registration.

Comparison of the brain motion before and after habituation of head fixation. (A–C) The brain motions of mouse 1–3 before and after habituation. Red circles indicate the in plane (X–Y) movements (10 pixels = 4.5 μm). (D) Histogram of the brain motions that larger than 4.5 μm before and after habituation (N = 4 mice, 8 focal planes). The habituation...

3D print file for head-post.

3D print file for recording holder.

3D print file for head-post holder.

Two-photon Ca²⁺ imaging has become a popular approach for monitoring neuronal population activity with cellular or subcellular resolution in vivo. This approach allows for the recording of hundreds to thousands of neurons per animal and thus leads to a large amount of data to be processed. In particular, manually drawing regions of interest is the...

Turing Machines are universal computing machines in theory. It has been a long debate whether Turing Machines can simulate the consciousness mind behaviors in the materialistic universe. Three different hypotheses come out of such debate, in short:(A) Can; (B) Cannot; (C) Super-Turing machines can. Because Turing Machines or other kinds of theoreti...

A long-standing objective in neuroscience has been to image distributed neuronal activity in freely behaving animals. Here we introduce NeuBtracker, a tracking microscope for simultaneous imaging of neuronal activity and behavior of freely swimming fluorescent reporter fish. We showcase the value of NeuBtracker for screening neurostimulants with re...

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational...

Background/aims: Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. Methods: A multi-center, random-order, double-blind taste study, SATIETY-1, was conducte...

Nonhuman primates provide an important model not only for understanding human brain but also for translational research in neurological and psychiatric disorders. However, many high-resolution techniques for recording neural activity in vivo that were initially established for rodents have not been yet applied to the nonhuman primate brain. Here, w...

Developments in miniaturized microscopes have enabled visualization of brain activities and structural dynamics in animals engaging in self-determined behaviors. However, it remains a challenge to resolve activity at single dendritic spines in freely behaving animals. Here, we report the design and application of a fast high-resolution, miniaturize...

Locomotion involves complex neural activity throughout different cortical and subcortical networks. The primary motor cortex (M1) receives a variety of projections from different brain regions and is responsible for executing movements. The primary visual cortex (V1) receives external visual stimuli and plays an important role in guiding locomotion...

The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior. Neocortical circuits for ongoing processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. We, therefore, used in...

Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments...

Significance We introduce a two-photon imaging method with improved depth penetration for the recording of neuronal activity with single-cell resolution in the intact brain of living animals. This method relies on the use of the fluorometric Ca ²⁺ -sensitive dye Cal-590, which is effectively excited by infrared light (1,050 nm). By combining popula...

Significance In the mammalian brain, sensory information reaches the cortex through thalamic axons, which provide a strong drive to layer 4 (L4). The thalamic inputs are characterized by their synchronous mode of activation and their high efficacy. Here, by using two-photon imaging in vivo, we analyze sensory-stimulation–evoked calcium transients o...

Mammalian cortical neurons integrate sensory information that arrives through numerous synaptic inputs located on their dendrites. Here we introduce an approach to identify sensory-evoked dendritic input sites in cortical neurons in vivo involving the use of two-photon calcium imaging combined with targeted whole-cell recordings. We provide basic t...

Layer 5 pyramidal neurons process information from multiple cortical layers to provide a major output of cortex. Because of technical limitations it has remained unclear how these cells integrate widespread synaptic inputs located in distantly separated basal and tuft dendrites. Here, we obtained in vivo two-photon calcium imaging recordings from t...

Neurons in the mammalian brain receive thousands of synaptic inputs on their dendrites. In many types of neurons, such as cortical pyramidal neurons, excitatory synapses are formed on fine dendritic protrusions called spines. Usually, an individual spine forms a single synaptic contact with an afferent axon. In this protocol, we describe a recently...