Integrative analysis of in vivo recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1

Vision formation is classically based on projections from retinal ganglion cells(RGC)to the lateral geniculate nucleus(LGN)and the primary visual cortex(V1).Neurons in the mouse V1 are tuned to light stimuli.Although the cellular information of the retina and the LGN has been widely studied,the transcriptome profiles of single light-stimulated neuron in V1 remain unknown.In our study,in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as lightsensitive(LS)or non-light-sensitive(NS)by single-cell light-evoked calcium evaluation and action potential spiking.The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing.Moreover,the three-dimensional(3-D)morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings.Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation,such as Rtn4r and Rgs7,and genes involved in membrane transport,such as Na+/K+ATPase and NMDA-type glutamatergic receptors,preferentially responded to light stimulation.Furthermore,an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice.In conclusion,our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

Hippocampal ischemia causes deficits in local field potential and synaptic plasticity

The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.

Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information

As a main structure of the limbic system,the hippocampus plays a critical role in pain perception and chronicity.The ventral hippocampal CA1(vCA1)is closely associated with negative emotions such as anxiety,stress,and fear,yet how vCA1 neurons encode nociceptive information remains unclear.Using in vivo electrophysiological recording,we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats.Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions:the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli,whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties.Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors.Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats,whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain.These results provide direct evidence for the representations of nociceptive information in vCA1.

A multi-channel fully differential programmable integrated circuit for neural recording application

A multi-channel, fully differential programmable chip for neural recording application is presented. The integrated circuit incorporates eight neural recording amplifiers with tunable bandwidth and gain, eight 4thorder Bessel switch capacitor filters, an 8-to-1 analog time-division multiplexer, a fully differential successive approximation register analog-to-digital converter （SAR ADC）, and a serial peripheral interface for communication. The neural recording amplifier presents a programmable gain from 53 dB to 68 dB, a tunable low cut-off frequency from 0.1 Hz to 300 Hz, and 3.77μVrms input-referred noise over a 5 kHz bandwidth. The SAR ADC digitizes signals at maximum sampling rate of 20 μS/s per channel and achieves an ENOB of 7.4. The integrated circuit is designed and fabricated in 0.18-μm CMOS mix-signal process. We successfully performed a multi-channel in-vivo recording experiment from a rat cortex using the neural recording chip.

Nerve-heart interplays recorded in rabbit hearts in vivo

Neurotransmitter release from presynaptic cells can be recorded by postsynaptic potentials/currents in central nerve system. However, little is known about how to

Methcathinone Increases Visually-evoked Neuronal Activity and Enhances Sensory Processing Efficiency in Mice

Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused worldwide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and empathy.However,little is known about how MCAT modulates neuronal activity in vivo.Here,we evaluated the effect of MCAT on neuronal activity with a series of functional approaches.C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold,especially in sensory and motor cortices,striatum,and midbrain motor nuclei.In vivo single-unit recording and two-photon Ca^(2+) imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration.Notably,MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability,specifically during a natural movie stimulus.It improved the information-processing efficiency by enhancing the single-neuron coding capacity,suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.

Plasticity of Sniffing Pattern and Neural Activity in the Olfactory Bulb of Behaving Mice During Odor Sampling,Anticipation,and Reward

The olfactory bulb(OB) is the first relay station in the olfactory system.In the OB,mitral/tufted cells(M/Ts),which are the main output neurons,play important roles in the processing and representation of odor information.Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning.Here,we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice.We used an odor discrimination task combined with in vivo electrophysiological recordings in awake,head-fixed mice,and found that,while learning induced plasticity of spikes and beta oscillations during odor sampling,we also found plasticity of spikes,beta oscillation,sniffing pattern,and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward.These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.

Local neuronal circuits that may shape the discharge patterns of inferior collicular neurons

The discharge patterns of neurons in auditory centers encode information about sounds.However,few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular recording techniques.Here,we investigated the discharge patterns of inferior collicular（IC）neurons using intracellular recordings to further elucidate the mechanisms underlying the shaping of discharge patterns.Under in vivo intracellular recording conditions,recordings were obtained from 66 IC neurons in 18 healthy adult mice（Mus musculus,Km）under free field-stimulation.Fiftyeight of these neurons fired bursts of action potentials（APs）to auditory stimuli and the remaining eight just generated local responses such as excitatory（n=4）or inhibitory（n=4）postsynaptic potentials.Based on the APs and subthreshold responses,the discharge patterns were classified into seven types：phasic（24/58,41.4%）,phasic burst（8/58,13.8%）,pauser（4/58,6.9%）,phasic-pauser（1/58,1.7%）,chopper（2/58,3.4%）,primary-like tonic（14/58,24.1%）and sound-induced inhibitory（5/58,8.6%）.We concluded that（1）IC neurons exhibit at least seven distinct discharge patterns;（2）inhibition participates in shaping the discharge pattern of most IC neurons and plays a role in sculpting the pattern,except for the primary-like tonic pattern which was not shapedby inhibition;and（3）local neural circuits are the likely structural basis that shapes the discharge patterns of IC neurons and can be formed either in the IC or in lower-level auditory structures.