Robert C. Liu

Acoustic variability and distinguishability among mouse ultrasound vocalizations

Auditory neurobiology has benefited significantly from ethological approaches using acoustic communication signals. Developing an ethological model in a genetically manipulable system such as the mouse would enhance the ability to investigate the processing, learning, and recognition of sounds. Characterizing the basic acoustic structure of mouse vocalizations would help lay a foundation for such a future study. Towards this goal, ultrasound vocalizations emitted by isolated mouse pups and pairs of adult males and females have been digitally recorded and examined. Previous work suggests that these calls may have communicative significance. An analysis of the natural variability in their spectral content, median frequency, duration, and repetition period reveals acoustic structure that could be used for recognizing the calls. Other parameters, like the rate of frequency modulation, may also be informative, but have not been examined. Pup isolation calls develop systematically between postnatal day 5 and 12 towards a more stereotyped vocalization--contracting from a wide range of values into narrower clusters of frequency and duration, and shifting from longer to shorter repetition periods. Most significantly, pup isolation and adult encounter calls fall into two distinct spectral and temporal categories, making it possible for a receiver to acoustically distinguish between them, and to potentially categorically perceive them along those dimensions.

Quantum interference in electron collision

The indistinguishability of identical quantum particles can lead to quantum interferences that profoundly affect their scattering. If two particles collide and scatter, the process that results in the detection of the first particle in one direction and the second particle in another direction interferes quantum mechanically with the physically indistinguishable process where the roles of the particles are reversed. For bosons such as photons, a constructive interference between probability amplitudes can enhance the probability, relative to classical expectations, that both are detected in the same direction — this is known as ‘bunching’. But for fermions such as electrons, a destructive interference should suppress this probability (‘anti-bunching’); this interference is the origin of the Pauli exclusion principle, which states that two electrons can never occupy the same state. Although two-particle interferences have been shown for colliding photons, no similar demonstration for electrons exists. Here we report the realization of this destructive quantum interference in the collision of electrons at a beam splitter. In our experiments, the quantum interference responsible for the Pauli exclusion principle is manifest as the suppression in electron current noise after collision.

Improved cortical entrainment to infant communication calls in mothers compared with virgin mice

There is a growing interest in the use of mice as a model system for species‐specific communication. In particular, ultrasonic calls emitted by mouse pups communicate distress, and elicit a search and retrieval response from mothers. Behaviorally, mothers prefer and recognize these calls in two‐alternative choice tests, in contrast to pup‐naïve females that do not have experience with pups. Here, we explored whether one particular acoustic feature that defines these calls − the repetition rate of calls within a bout − is represented differently in the auditory cortex of these two animal groups. Multiunit recordings in anesthetized CBA/CaJ mice revealed that: (i) neural entrainment to repeated stimuli extended up to the natural pup call repetition rate (5 Hz) in mothers; but (ii) neurons in naïve females followed repeated stimuli well only at slower repetition rates; and (iii) entrained responses to repeated pup calls were less sensitive to natural pup call variability in mothers than in pup‐naïve females. In the broader context, our data suggest that auditory cortical responses to communication sounds are plastic, and that communicative significance is correlated with an improved cortical representation.

Inhibitory synaptic plasticity: spike timing-dependence and putative network function

While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

Dissecting natural sensory plasticity: Hormones and experience in a maternal context

There is a growing consensus that the auditory system is dynamic in its representation of behaviorally relevant sounds. The auditory cortex in particular seems to be an important locus for plasticity that may reflect the memory of such sounds, or functionally improve their processing. The mechanisms that underlie these changes may be either intrinsic because they depend on the receivers physiological state, or extrinsic because they arise from the context in which behavioral relevance is gained. Research in a mouse model of acoustic communication between offspring and adult females offers the opportunity to explore both of these contributions to auditory cortical plasticity in a natural context. Recent works have found that after the vocalizations of infant mice become behaviorally relevant to mothers, auditory cortical activity is significantly changed in a way that may improve their processing. Here we consider the hypothesis that maternal hormones (intrinsic factor) and sensory experience (extrinsic factor) contribute together to drive these changes, focusing specifically on the evidence that well-known experience-dependent mechanisms of cortical plasticity can be modulated by hormones.

Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles

Adult pair bonding involves dramatic changes in the perception and valuation of another individual. One key change is that partners come to reliably activate the brain’s reward system, although the precise neural mechanisms by which partners become rewarding during sociosexual interactions leading to a bond remain unclear. Here we show, using a prairie vole (Microtus ochrogaster) model of social bonding, how a functional circuit from the medial prefrontal cortex to nucleus accumbens is dynamically modulated to enhance females’ affiliative behaviour towards a partner. Individual variation in the strength of this functional connectivity, particularly after the first mating encounter, predicts how quickly animals begin affiliative huddling with their partner. Rhythmically activating this circuit in a social context without mating biases later preference towards a partner, indicating that this circuit’s activity is not just correlated with how quickly animals become affiliative but causally accelerates it. These results provide the first dynamic view of corticostriatal activity during bond formation, revealing how social interactions can recruit brain reward systems to drive changes in affiliative behaviour.

Storing maternal memories: Hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues

Much of the literature on maternal behavior has focused on the role of infant experience and hormones in a canonical subcortical circuit for maternal motivation and maternal memory. Although early studies demonstrated that the cerebral cortex also plays a significant role in maternal behaviors, little has been done to explore what that role may be. Recent work though has provided evidence that the cortex, particularly sensory cortices, contains correlates of sensory memories of infant cues, consistent with classical studies of experience-dependent sensory cortical plasticity in non-maternal paradigms. By reviewing the literature from both the maternal behavior and sensory cortical plasticity fields, focusing on the auditory modality, we hypothesize that maternal hormones (predominantly estrogen) may act to prime auditory cortical neurons for a longer-lasting neural trace of infant vocal cues, thereby facilitating recognition and discrimination. This couldthen more efficiently activate the subcortical circuit to elicit and sustain maternal behavior.

A role for maternal physiological state in preserving auditory cortical plasticity for salient infant calls.

A growing interest in sensory system plasticity in the natural context of motherhood has created the need to investigate how intrinsic physiological state (e.g., hormonal, motivational, etc.) interacts with sensory experience to drive adaptive cortical plasticity for behaviorally relevant stimuli. Using a maternal mouse model of auditory cortical inhibitory plasticity for ultrasonic pup calls, we examined the role of pup care versus maternal physiological state in the long-term retention of this plasticity. Very recent experience caring for pups by Early Cocarers, which are virgins, produced stronger call-evoked lateral-band inhibition in auditory cortex. However, this plasticity was absent when measured post-weaning in Cocarers, even though it was present at the same time point in Mothers, whose pup experience occurred under a maternal physiological state. A two-alternative choice phonotaxis task revealed that the same animal groups (Early Cocarers and Mothers) demonstrating stronger lateral-band inhibition also preferred pup calls over a neutral sound, a correlation consistent with the hypothesis that this inhibitory mechanism may play a mnemonic role and is engaged to process sounds that are particularly salient. Our electrophysiological data hint at a possible mechanism through which the maternal physiological state may act to preserve the cortical plasticity: selectively suppressing detrimental spontaneous activity in neurons that are responsive to calls, an effect observed only in Mothers. Taken together, the maternal physiological state during the care of pups may help maintain the memory trace of behaviorally salient infant cues within core auditory cortex, potentially ensuring a more rapid induction of future maternal behavior.

Norepinephrine is necessary for experience-dependent plasticity in the developing mouse auditory cortex.

Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this windows importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine β-hydroxylase knock-out (Dbh−/−) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh−/− mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex.

Behavioral Relevance Helps Untangle Natural Vocal Categories in a Specific Subset of Core Auditory Cortical Pyramidal Neurons

Sound categorization is essential for auditory behaviors like acoustic communication, but its genesis within the auditory pathway is not well understood—especially for learned natural categories like vocalizations, which often share overlapping acoustic features that must be distinguished (e.g., speech). We use electrophysiological mapping and single-unit recordings in mice to investigate how representations of natural vocal categories within core auditory cortex are modulated when one category acquires enhanced behavioral relevance. Taking advantage of a maternal mouse model of acoustic communication, we found no long-term auditory cortical map expansion to represent a behaviorally relevant pup vocalization category—contrary to expectations from the cortical plasticity literature on conditioning with pure tones. Instead, we observed plasticity that improved the separation between acoustically similar pup and adult vocalization categories among a physiologically defined subset of late-onset, putative pyramidal neurons, but not among putative interneurons. Additionally, a larger proportion of these putative pyramidal neurons in maternal animals compared with nonmaternal animals responded to the individual pup call exemplars having combinations of acoustic features most typical of that category. Together, these data suggest that higher-order representations of acoustic categories arise from a subset of core auditory cortical pyramidal neurons that become biased toward the combination of acoustic features statistically predictive of membership to a behaviorally relevant sound category.