Jumpei Matsumoto

Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes

Significance The present study shows preferential activity of neurons in the medial and dorsolateral pulvinar to images of snakes. Pulvinar neurons responded faster and stronger to snake stimuli than to monkey faces, monkey hands, and geometric shapes, and were sensitive to unmodified and low-pass filtered images but not to high-pass filtered images. These results identify a neurobiological substrate for rapid detection of threatening visual stimuli in primates. Our findings are unique in providing neuroscientific evidence in support of the Snake Detection Theory, which posits that the threat of snakes strongly influenced the evolution of the primate brain. This finding may have great impact on our understanding of the evolution of primates. Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates’ heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

Neuronal responses to face-like stimuli in the monkey pulvinar.

The pulvinar nuclei appear to function as the subcortical visual pathway that bypasses the striate cortex, rapidly processing coarse facial information. We investigated responses from monkey pulvinar neurons during a delayed non‐matching‐to‐sample task, in which monkeys were required to discriminate five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face‐like patterns (three dark blobs on a bright oval), eye‐like patterns and simple geometric patterns]. Of 401 neurons recorded, 165 neurons responded differentially to the visual stimuli. These visual responses were suppressed by scrambling the images. Although these neurons exhibited a broad response latency distribution, face‐like patterns elicited responses with the shortest latencies (approximately 50 ms). Multidimensional scaling analysis indicated that the pulvinar neurons could specifically encode face‐like patterns during the first 50‐ms period after stimulus onset and classify the stimuli into one of the five different categories during the next 50‐ms period. The amount of stimulus information conveyed by the pulvinar neurons and the number of stimulus‐differentiating neurons were consistently higher during the second 50‐ms period than during the first 50‐ms period. These results suggest that responsiveness to face‐like patterns during the first 50‐ms period might be attributed to ascending inputs from the superior colliculus or the retina, while responsiveness to the five different stimulus categories during the second 50‐ms period might be mediated by descending inputs from cortical regions. These findings provide neurophysiological evidence for pulvinar involvement in social cognition and, specifically, rapid coarse facial information processing.

Neuronal responses to face-like and facial stimuli in the monkey superior colliculus.

The superficial layers of the superior colliculus (sSC) appear to function as a subcortical visual pathway that bypasses the striate cortex for the rapid processing of coarse facial information. We investigated the responses of neurons in the monkey sSC during a delayed non-matching-to-sample (DNMS) task in which monkeys were required to discriminate among five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns, and simple geometric patterns]. Of the 605 sSC neurons recorded, 216 neurons responded to the visual stimuli. Among the stimuli, face-like patterns elicited responses with the shortest latencies. Low-pass filtering of the images did not influence the responses. However, scrambling of the images increased the responses in the late phase, and this was consistent with a feedback influence from upstream areas. A multidimensional scaling (MDS) analysis of the population data indicated that the sSC neurons could separately encode face-like patterns during the first 25-ms period after stimulus onset, and stimulus categorization developed in the next three 25-ms periods. The amount of stimulus information conveyed by the sSC neurons and the number of stimulus-differentiating neurons were consistently higher during the 2nd to 4th 25-ms periods than during the first 25-ms period. These results suggested that population activity of the sSC neurons preferentially filtered face-like patterns with short latencies to allow for the rapid processing of coarse facial information and developed categorization of the stimuli in later phases through feedback from upstream areas.

Social buffering suppresses fear-associated activation of the lateral amygdala in male rats: behavioral and neurophysiological evidence

In social mammals, the presence of an affiliative conspecific reduces stress responses, a phenomenon referred to as “social buffering.”In a previous study, we found that the presence of a conspecific animal ameliorated a variety of stress responses to an aversive conditioned stimulus (CS), including freezing and Fos expression in the lateral amygdala (LA) of male rats. Although these findings suggest that the presence of a conspecific animal suppresses neural activity in the LA, direct neurophysiological evidence of suppressed activity in the LA during social buffering is still lacking. In the present study, we analyzed freezing behavior and local field potentials in the LA of fear-conditioned rats in response to the CS, in the presence or absence of a conspecific. After auditory aversive conditioning, the CS was presented to the conditioned rats in the presence or absence of a conspecific animal, on 2 successive days. The presence of a conspecific animal significantly decreased the mean peak amplitudes of auditory evoked field potentials, gamma oscillations (25–75 Hz) and high frequency oscillations (100–300 Hz) in the LA. Furthermore, magnitudes of these neural responses positively correlated with freezing duration of the fear-conditioned rats. The results provide the first electrophysiological evidence that social buffering suppresses CS-induced activation in the LA, which consequently reduces conditioned fear responses.

A 3D-Video-Based Computerized Analysis of Social and Sexual Interactions in Rats

A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior.

Relationships among parvalbumin-immunoreactive neuron density, phase-locked gamma oscillations, and autistic/schizophrenic symptoms in PDGFR-β knock-out and control mice.

Cognitive deficits and negative symptoms are important therapeutic targets for schizophrenia and autism disorders. Although reduction of phase-locked gamma oscillation has been suggested to be a result of reduced parvalbumin-immunoreactive (putatively, GABAergic) neurons, no direct correlations between these have been established in these disorders. In the present study, we investigated such relationships during pharmacological treatment with a newly synthesized drug, T-817MA, which displays neuroprotective and neurotrophic effects. In this study, we used platelet-derived growth factor receptor-β gene knockout (PDGFR-β KO) mice as an animal model of schizophrenia and autism. These mutant mice display a reduction in social behaviors; deficits in prepulse inhibition (PPI); reduced levels of parvalbumin-immunoreactive neurons in the medical prefrontal cortex, hippocampus, amygdala, and superior colliculus; and a deficit in of auditory phase-locked gamma oscillations. We found that oral administration of T-817MA ameliorated all these symptoms in the PDGFR-β KO mice. Furthermore, phase-locked gamma oscillations were significantly correlated with the density of parvalbumin-immunoreactive neurons, which was, in turn, correlated with PPI and behavioral parameters. These findings suggest that recovery of parvalbumin-immunoreactive neurons by pharmacological intervention relieved the reduction of phase-locked gamma oscillations and, consequently, ameliorated PPI and social behavioral deficits. Thus, our findings suggest that phase-locked gamma oscillations could be a useful physiological biomarker for abnormality of parvalbumin-immunoreactive neurons that may induce cognitive deficits and negative symptoms of schizophrenia and autism, as well as of effective pharmacological interventions in both humans and experimental animals.

Neuronal Responses in the Nucleus Accumbens Shell during Sexual Behavior in Male Rats

Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation.

Snakes elicit earlier, and monkey faces, later, gamma oscillations in macaque pulvinar neurons

Gamma oscillations (30–80 Hz) have been suggested to be involved in feedforward visual information processing, and might play an important role in detecting snakes as predators of primates. In the present study, we analyzed gamma oscillations of pulvinar neurons in the monkeys during a delayed non-matching to sample task, in which monkeys were required to discriminate 4 categories of visual stimuli (snakes, monkey faces, monkey hands and simple geometrical patterns). Gamma oscillations of pulvinar neuronal activity were analyzed in three phases around the stimulus onset (Pre-stimulus: 500 ms before stimulus onset; Early: 0–200 ms after stimulus onset; and Late: 300–500 ms after stimulus onset). The results showed significant increases in mean strength of gamma oscillations in the Early phase for snakes and the Late phase for monkey faces, but no significant differences in ratios and frequencies of gamma oscillations among the 3 phases. The different periods of stronger gamma oscillations provide neurophysiological evidence that is consistent with other studies indicating that primates can detect snakes very rapidly and also cue in to faces for information. Our results are suggestive of different roles of gamma oscillations in the pulvinar: feedforward processing for images of snakes and cortico-pulvinar-cortical integration for images of faces.

Monkey pulvinar neurons fire differentially to snake postures.

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems.

Effects of the neurotrophic agent T-817MA on oligomeric amyloid-β-induced deficits in long-term potentiation in the hippocampal CA1 subfield.

Formation of oligomeric amyloid-β (oAβ) is 1 of the most likely causes of Alzheimers disease (AD). We hypothesized that in the early phase of AD, cognitive impairments observed before marked neuronal loss and brain atrophy might be associated with oAβ-induced synaptic dysfunction. T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] has both neuroprotective and neurotrophic effects and is used to treat AD. Although T-817MA has been shown to ameliorate amyloid-induced learning deficits in experimental AD models, it remains unclear whether this drug would be able to prevent oAβ-induced synaptotoxicity. In the present study, we investigated the effects of T-817MA on the disturbances in synaptic plasticity induced by oAβ42 and oligomeric photo-cross-linked Aβ42 (oXLAβ42) in a slice preparation of the CA1 subfield of mouse hippocampus. Both oAβ42 and oXLAβ42 treatments significantly reduced the induction of long-term potentiation (LTP). In addition, oAβ42 treatment significantly facilitated long-term depression (LTD). Treatment with T-817MA ameliorated the LTP reduction; however, T-817MA treatment did not inhibit the facilitation of LTD induction by oAβ42. These results suggest that T-817MA reverses oAβ-induced LTP reduction as it may occur in the early phase of AD.