Although Hebbian LTP has an important role in memory formation, the properties of Hebbian LTP cannot fully account for, and in some cases seem incompatible with, fundamental properties of associative learning. Importantly, findings from computational and neurophysiological studies suggest that burst-dependent forms of plasticity, where dendritic spikes and bursts of action potentials provide the postsynaptic depolarization needed for LTP induction, may overcome some of the limitations of conventional Hebbian LTP. Thus, I investigated how excitatory synapses onto CA1 pyramidal cells interact during the induction of complex spike (CS) burst-dependent LTP in hippocampal slices from male mice. Consistent with previous findings, theta-frequency trains of synaptic stimulation induce a Hebbian form of plasticity where postsynaptic CS bursts provide the depolarization needed for NMDAR activation and LTP induction. However, in contrast to conventional Hebbian plasticity, where cooperative LTP induction requires coa...

DRG neurons are classified into distinct types to mediate the somatosensation with different modalities. Recently, transcriptional profilings of DRG neurons by single-cell RNA-sequencing have provided new insights into the neuron typing and functional properties. Zinc-finger CCHC domain-containing 12 ( Zcchc12 ) was reported to be the representative marker for a subtype of galanin-positive ( Gal +) DRG neurons. However, the characteristics and functions of Zcchc12 + neurons are largely unknown. Here, we genetically labeled Zcchc12 + neurons in Zcchc12 -CreERT2::Ai9 mice, and verified that Zcchc12 represented a new subpopulation of DRG neurons in both sexes. Zcchc12 + neurons centrally innervated the superficial laminae in spinal dorsal horn, and peripherally terminated as free nerve endings in the epidermis and cluster-shaped fibers in the dermis of footpads and nearby. In addition, Zcchc12 + neurons also formed circumferential endings surrounding the hair follicles in hairy skin. Functionally, in vivo cal...

Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners control signal convergence and divergence in neural circuits. The developmental mechanisms that determine cell-type-specific dendrite and axon size and match synaptic partners' arbor territories remain obscure. Here, we discover that retinal horizontal cells express the leucine-rich repeat domain cell adhesion molecule AMIGO1. Horizontal cells provide pathway-specific feedback to photoreceptors—horizontal cell axons to rods and horizontal cell dendrites to cones. AMIGO1 selectively expands the size of horizontal cell axons. When Amigo1 is deleted in all or individual horizontal cells of either sex, their axon arbors shrink. By contrast, horizontal cell dendrites and synapse formation of horizontal cell axons and dendrites are unaffected by AMIGO1 removal. The dendrites of rod bipolar cells, which do not express AMIGO1, shrink in parallel w...

Multimodal integration facilitates object recognition and response to sensory cues. This depends on spatiotemporal coincidence of sensory information, recruitment of NMDA-type glutamate receptors and inhibitory feedback. Shepherd's crook neurons (SCNs) in the avian optic tectum (TeO) are an ideal model for studying cellular mechanism of multimodal integration. They receive different sensory modalities through spatially segregated dendrites, are important for stimulus selection and have an axon-carrying dendrite (AcD). We performed whole-cell patch-clamp experiments in chicken midbrain slices of both sexes. We emulated visual and auditory input in vitro by stimulating presynaptic afferents electrically. Simultaneous stimulation enhanced responses inversely depending on stimulation amplitude demonstrating the principle of inverse effectiveness. Contribution of NMDA-type glutamate receptors prolonged postsynaptic events for visual inputs only, causing a strong modality-specific difference in synaptic efficacy...

Chuangeng Zhang, Meijian Wang, Shengyin Lin, and Ruili Xie (see pages [2729–2742][1]) Auditory nerve fibers are categorized by their spontaneous spike rate and auditory threshold, and they differ in their expression of the calcium binding protein calretinin (CR). Whereas low-threshold/high-

Neurophysiological work in primates and rodents have shown the amygdala plays a central role in reward processing through connectivity with the orbitofrontal cortex (OFC) and hippocampus. However, understanding the role of oscillations in each region and their connectivity in different stages of reward processing in humans has been hampered by limitations with noninvasive methods such as poor spatial and temporal resolution. To overcome these limitations, we recorded local field potentials (LFPs) directly from the amygdala, OFC and hippocampus simultaneously in human male and female epilepsy patients performing a monetary incentive delay (MID) task. This allowed us to dissociate electrophysiological activity and connectivity patterns related to the anticipation and receipt of rewards and losses in real time. Anticipation of reward increased high-frequency gamma (HFG; 60–250 Hz) activity in the hippocampus and theta band (4–8 Hz) synchronization between amygdala and OFC, suggesting roles in memory and motiv...

The ventral striatum is implicated in the affective processing of reward, which can be divided into a motivational and a hedonic component. Here, we examined whether these two components rely on distinct neural substrates within the ventral striatum in humans (11 females and 13 males). We used a high-resolution fMRI protocol targeting the ventral striatum combined with a pavlovian-instrumental task and a hedonic reactivity task. Both tasks involved an olfactory reward, thereby allowing us to measure pavlovian-triggered motivation and sensory pleasure for the same reward within the same participants. Our findings show that different subregions of the ventral striatum are dissociable in their contributions to the motivational versus the hedonic component of the affective processing of reward. Parsing the neural mechanisms of the interplay between pavlovian incentive and hedonic processes may have important implications for understanding compulsive reward-seeking behaviors such as addiction, binge eating, or ...

Calretinin (CR) is a major calcium binding protein widely expressed in the CNS. However, its synaptic function remains largely elusive. At the auditory synapse of the endbulb of Held, CR is selectively expressed in different subtypes. Combining electrophysiology with immunohistochemistry, we investigated the synaptic transmission at the endbulb of Held synapses with and without endogenous CR expression in mature CBA/CAJ mice of either sex. Two synapse subtypes showed similar basal synaptic transmission, except a larger quantal size in CR-expressing synapses. During high-rate stimulus trains, CR-expressing synapses showed improved synaptic efficacy with significantly less depression and lower asynchronous release, suggesting more efficient exocytosis than non-CR-expressing synapses. Conversely, CR-expressing synapses had a smaller readily releasable pool size, which was countered by higher release probability and faster synaptic recovery to support sustained release during high-rate activity. EGTA-AM treatm...

Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli also modulate neuronal activity in somatosensory cortices of the ipsilateral hemisphere. The cellular organization and functional role of these ipsilateral stimulus responses in awake somatosensory cortices, especially regarding stimulus coding, are unknown. Here, we targeted silicon probe recordings to the vibrissa region of primary (S1) and secondary (S2) somatosensory cortex of awake head-fixed mice of either sex while delivering ipsilateral and contralateral whisker stimuli. Ipsilateral stimuli drove larger and more reliable responses in S2 than in S1, and activated a larger fraction of stimulus-responsive neurons. Ipsilateral stimulus-responsive neurons were rare in layer 4 of S1, but were located in equal proportion across all layers in S2. Linear classifier analyses further revealed that decoding of the ipsilateral stimulus was more a...