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Neural circuitry for maternal oxytocin release induced by infant cries
Valtcheva, Silvana; Issa, Habon A; Bair-Marshall, Chloe J; Martin, Kathleen A; Jung, Kanghoon; Zhang, Yiyao; Kwon, Hyung-Bae; Froemke, Robert C
Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing1-6. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers7, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.
PMCID:10639004
PMID: 37730989
ISSN: 1476-4687
CID: 5607312
Locus coeruleus activity improves cochlear implant performance
Glennon, Erin; Valtcheva, Silvana; Zhu, Angela; Wadghiri, Youssef Z; Svirsky, Mario A; Froemke, Robert C
Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people1. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable2,3. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes4-7. Despite extensive studies on how CIs activate the auditory system4,8-12, the understanding of CI-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator noradrenaline from the brainstem locus coeruleus (LC). Here we examine behavioural responses and neural activity in LC and auditory cortex of deafened rats fitted with multi-channel CIs. The rats were trained on a reward-based auditory task, and showed considerable individual differences of learning rates and maximum performance. LC photometry predicted when CI subjects began responding to sounds and longer-term perceptual accuracy. Optogenetic LC stimulation produced faster learning and higher long-term accuracy. Auditory cortical responses to CI stimulation reflected behavioural performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically relevant target for optimizing neuroprosthetic device use.
PMID: 36544024
ISSN: 1476-4687
CID: 5395022
Contributions of cortical neuron firing patterns, synaptic connectivity, and plasticity to task performance
Insanally, Michele N; Albanna, Badr F; Toth, Jade; DePasquale, Brian; Fadaei, Saba Shokat; Gupta, Trisha; Lombardi, Olivia; Kuchibhotla, Kishore; Rajan, Kanaka; Froemke, Robert C
Neuronal responses during behavior are diverse, ranging from highly reliable 'classical' responses to irregular 'non-classically responsive' firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity. Reliable and irregular units contribute differentially to task performance via output and recurrent connections, respectively. Excitatory plasticity shifts the response distribution while inhibition constrains its diversity. Together both improve task performance with full network engagement. The same local patterns of synaptic inputs predict spiking response properties of network units and auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus, diverse neural responses contribute to network function and emerge from synaptic plasticity rules.
PMCID:11255273
PMID: 39019848
ISSN: 2041-1723
CID: 5699362
Oxytocin neurons enable social transmission of maternal behaviour
Carcea, Ioana; Caraballo, Naomi López; Marlin, Bianca J; Ooyama, Rumi; Riceberg, Justin S; Mendoza Navarro, Joyce M; Opendak, Maya; Diaz, Veronica E; Schuster, Luisa; Alvarado Torres, Maria I; Lethin, Harper; Ramos, Daniel; Minder, Jessica; Mendoza, Sebastian L; Bair-Marshall, Chloe J; Samadjopoulos, Grace H; Hidema, Shizu; Falkner, Annegret; Lin, Dayu; Mar, Adam; Wadghiri, Youssef Z; Nishimori, Katsuhiko; Kikusui, Takefumi; Mogi, Kazutaka; Sullivan, Regina M; Froemke, Robert C
Maternal care, including by non-biological parents, is important for offspring survival1-8. Oxytocin1,2,9-15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress15. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.
PMID: 34381215
ISSN: 1476-4687
CID: 4972632
Oxytocin, Neural Plasticity, and Social Behavior
Froemke, Robert C; Young, Larry J
Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo. These studies indicate that oxytocin can enhance the salience of social stimuli and increase signal-to-noise ratios by modulating spiking and synaptic plasticity in the context of circuits and networks. We highlight oxytocin effects on social behavior in nontraditional organisms such as prairie voles and discuss opportunities to enhance the utility of these organisms for studying circuit-level modulation of social behaviors. We then discuss recent insights into oxytocin neuron activity during social interactions. We conclude by discussing some of the major questions and opportunities in the field ahead.
PMID: 33823654
ISSN: 1545-4126
CID: 4976412
Innate and plastic mechanisms for maternal behaviour in auditory cortex
Schiavo, Jennifer K; Valtcheva, Silvana; Bair-Marshall, Chloe J; Song, Soomin C; Martin, Kathleen A; Froemke, Robert C
Infant cries evoke powerful responses in parents1-4. Whether parental animals are intrinsically sensitive to neonatal vocalizations, or instead learn about vocal cues for parenting responses is unclear. In mice, pup-naive virgin females do not recognize the meaning of pup distress calls, but retrieve isolated pups to the nest after having been co-housed with a mother and litter5-9. Distress calls are variable, and require co-caring virgin mice to generalize across calls for reliable retrieval10,11. Here we show that the onset of maternal behaviour in mice results from interactions between intrinsic mechanisms and experience-dependent plasticity in the auditory cortex. In maternal females, calls with inter-syllable intervals (ISIs) from 75 to 375Â milliseconds elicited pup retrieval, and cortical responses were generalized across these ISIs. By contrast, naive virgins were neuronally and behaviourally sensitized to the most common ('prototypical') ISIs. Inhibitory and excitatory neural responses were initially mismatched in the cortex of naive mice, with untuned inhibition and overly narrow excitation. During co-housing experiments, excitatory responses broadened to represent a wider range of ISIs, whereas inhibitory tuning sharpened to form a perceptual boundary. We presented synthetic calls during co-housing and observed that neurobehavioural responses adjusted to match these statistics, a process that required cortical activity and the hypothalamic oxytocin system. Neuroplastic mechanisms therefore build on an intrinsic sensitivity in the mouse auditory cortex, and enable rapid plasticity for reliable parenting behaviour.
PMID: 33029014
ISSN: 1476-4687
CID: 4651762
Heterosynaptic Plasticity Determines the Set Point for Cortical Excitatory-Inhibitory Balance
Field, Rachel E; D'amour, James A; Tremblay, Robin; Miehl, Christoph; Rudy, Bernardo; Gjorgjieva, Julijana; Froemke, Robert C
Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or balanced with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses or about the mechanisms for establishing or maintaining this balance at specific set points. Here we show how coordinated long-term plasticity calibrates populations of excitatory-inhibitory inputs onto mouse auditory cortical pyramidal neurons. Pairing pre- and postsynaptic activity induced plasticity at paired inputs and different forms of heterosynaptic plasticity at the strongest unpaired synapses, which required minutes of activity and dendritic Ca2+ signaling to be computed. Theoretical analyses demonstrated how the relative rate of heterosynaptic plasticity could normalize and stabilize synaptic strengths to achieve any possible excitatory-inhibitory correlation. Thus, excitatory-inhibitory balance is dynamic and cell specific, determined by distinct plasticity rules across multiple excitatory and inhibitory synapses.
PMID: 32213321
ISSN: 1097-4199
CID: 4358042
Oxytocin enables maternal behavior by balancing cortical inhibition [Meeting Abstract]
Marlin, B J; Mitre, M; Carcea, L; D'Amour, J A; Schiavo, J; Chao, M V; Froemke, R C
Background: Oxytocin is essential for social interactions and maternal behavior. However, little is known about how oxytocin modulates neural circuits to improve social and maternal outcomes. We describe a synaptic mechanism by which oxytocin enhances signal-to-noise ratio in left primary auditory cortex to improve mouse maternal behavior. Methods: We performed electrophysiological recordings, and used anatomical, optogenetic and behavioral techniques to examine the role of oxytocin in maternal behavior in wild-type C57BL/6 and Oxytocin-IRES-Cre mice. Results: Virgins females, who do not initially retrieve distressed pups, rapidly expressed retrieval behavior after receiving oxytocin under dam and pups co-housing conditions. Retrieval onset was accelerated in 20/36 mice receiving systemic oxytocin and in 5/7 mice receiving optogenetic stimulation (P=0.03, 0.05, respectively; Fisher's two-tailed exact test). To confirm regional sites of action subserving improved maternal behavior, we generated novel antibodies that bind to the mouse oxytocin receptor. Oxytocin receptors were preferentially expressed in the left auditory cortex (19% left cells, 14% right cells, n=21, P=0.001). Finally, we utilitzed in vivo whole-cell recordings to measure spiking/synaptic responses to pup calls. Pup call responses were lateralized, with co-tuned/temporally-precise responses in left auditory cortex of maternally-experienced but not maternal-naive adults. Pairing calls with oxytocin enhanced call-evoked responses in virgin dams by balancing the magnitude/ timing of inhibition with excitation, transitioning the auditory cortex from a virgin-like state to a maternal state. Conclusions: Our study provides a biological basis for the lateralization of vocal processing and emergence of experience-based social learning. These studies inform behavioral therapies involving oxytocin administration
EMBASE:72256862
ISSN: 0006-3223
CID: 2103542
Encoding the glucose identity by discrete hypothalamic neurons via the gut-brain axis
Kim, Jineun; Kim, Shinhye; Jung, Wongyo; Kim, Yujin; Lee, Seongju; Kim, Sehun; Park, Hae-Yong; Yoo, Dae Young; Hwang, In Koo; Froemke, Robert C; Lee, Seung-Hee; Park, Young-Gyun; Schwartz, Gary J; Suh, Greg S B
Animals need daily intakes of three macronutrients: sugar, protein, and fat. Under fasted conditions, however, animals prioritize sugar as a primary source of energy. They must detect ingested sugar-specifically D-glucose-and quickly report its presence to the brain. Hypothalamic neurons that can respond to the caloric content in the gut regardless of the identity of macronutrient have been identified, but until now, the existence of neurons that can encode the specific macronutrients remained unknown. We found that a subset of corticotropin-releasing factor (CRF)-expressing neurons in the hypothalamic paraventricular nucleus (CRFPVN) respond specifically to D-glucose in the gut, separately from other macronutrients or sugars. CRFPVN neuronal activity is essential for fasted mice to develop a preference for D-glucose. These responses of CRFPVN neurons to intestinal D-glucose require a specific spinal gut-brain pathway including the dorsal lateral parabrachial nuclei. These findings reveal the neural circuit that encodes the identity of D-glucose.
PMID: 40543511
ISSN: 1097-4199
CID: 5871472
Lateralized local circuit tuning in female mouse auditory cortex
Song, Soomin C; Froemke, Robert C
Most offspring are born helpless, requiring intense caregiving from parents especially during the first few days of neonatal life. For many species, infant cries are a primary signal used by parents to provide caregiving. Previously we and others documented how maternal left auditory cortex rapidly becomes sensitized to pup calls over hours of parental experience, enabled by oxytocin. The speed and robustness of this maternal plasticity suggests cortical pre-tuning or initial bias for pup call stimulus features. Here we examine the circuit basis of left-lateralized tuning to vocalization features with whole-cell recordings in brain slices. We found that layer 2/3 pyramidal cells of female left auditory cortex show selective suppression of inhibitory inputs with repeated stimulation at the fundamental pup call rate (inter-stimulus interval ∼150 msec) in pup-naïve females and expanded with maternal experience. However, optogenetic stimulation of cortical inhibitory cells showed that inputs from somatostatin-positive and oxytocin-receptor-expressing interneurons were less suppressed at these rates. This suggested that disynaptic inhibition rather than monosynaptic depression was a major mechanism underlying pre-tuning of cortical excitatory neurons, confirmed with simulations. Thus cortical interneuron specializations can augment neuroplasticity mechanisms to ensure fast appropriate caregiving in response to infant cries.
PMID: 40189152
ISSN: 1872-8111
CID: 5823522