An official website of the United States government
Abstract Neuronal plasticity can vary remarkably in its form and degree across animal species. Adult neurogenesis, namely the capacity to produce new neurons from neural stem cells through adulthood, appears widespread in non-mammalian vertebrates, whereas it is reduced in mammals. A growing body of comparative studies also report variation in the occurrence and activity of neural stem cell niches between mammals, with a general trend of reduction from small-brained to large-brained species. Conversely, recent studies have shown that large-brained mammals host large amounts of neurons expressing typical markers of neurogenesis in the absence of cell division. In layer II of the cerebral cortex, populations of prenatally generated, non-dividing neurons continue to express molecules indicative of immaturity throughout life (cortical immature neurons; cINs). After remaining in a dormant state for a very long time, these cINs retain the potential of differentiating into mature neurons that integrate within the preexisting neural circuits. They are restricted to the paleocortex in small-brained rodents, while extending into the widely expanded neocortex of highly gyrencephalic, large-brained species. The current hypothesis is that these populations of non-newly generated “immature” neurons might represent a reservoir of developmentally plastic cells for mammalian species that are characterized by reduced stem cell-driven adult neurogenesis. This indicates that there may be a trade-off between various forms of plasticity that coexist during brain evolution. This balance may be necessary to maintain a “reservoir of plasticity” in brain regions that have distinct roles in species-specific socioecological adaptations, such as the neocortex and olfactory structures.
more »
« less
This content will become publicly available on August 14, 2026
Multispecies characterization of immature neurons in the mammalian amygdala reveals their expansion in primates
Structural changes involving new neurons can occur through stem cell-driven neurogenesis, and through incorporation of late-maturing “immature” neurons into networks, namely undifferentiated neuronal precursors frozen in a state of arrested maturation. The latter have been found in the cerebral cortex and are particularly abundant in large-brained mammals, covarying with the size of the brain and cortex. Similar cells have been described in the amygdala of some species, although their features and interspecies variation remain poorly understood. Here, their occurrence, number, morphology, molecular expression, age-related changes, and anatomical distribution in amygdala subdivisions were systematically analyzed in eight diverse mammalian species (including mouse, naked mole rat, rabbit, marmoset, cat, sheep, horse, and chimpanzee) widely differing in neuroanatomy, brain size, life span, and socioecology. We identify converging evidence that these amygdala cells are immature neurons and show marked phylogenetic variation, with a significantly greater prevalence in primates. The immature cells are largely located within the amygdala’s basolateral complex, a region that has expanded in primate brain evolution in conjunction with cortical projections. In addition, amygdala immature neurons also appear to stabilize in number through adulthood and old age, unlike other forms of plasticity that undergo marked age-related reduction. These results support the emerging view that large brains performing complex socio-cognitive functions rely on wide reservoirs of immature neurons.
more »
« less
- Award ID(s):
- 2021785
- PAR ID:
- 10644324
- Editor(s):
- Fudge, Julie
- Publisher / Repository:
- PLOS
- Date Published:
- Journal Name:
- PLOS Biology
- Volume:
- 23
- Issue:
- 8
- ISSN:
- 1545-7885
- Page Range / eLocation ID:
- e3003322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on “engrams” in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience-dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity-dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP− neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.more » « less
-
Abstract The brain is organized into intrinsically connected functional networks that can be reliably identified during resting-state functional magnetic resonance imaging (fMRI). Healthy aging is marked by decreased network segregation, which is linked to worse cognitive functioning, but aging-related changes in emotion are less well characterized. Valence bias, which represents the tendency to interpret emotionally ambiguous information as positive or negative, is more positive in older than younger adults and is associated with differences in task-based fMRI activation in the amygdala, prefrontal cortex, and a cingulo-opercular (CO) network. Here, we examined valence bias, age, and resting-state network segregation of 12 brain networks in a sample of 221 healthy individuals from 6 to 80 years old. Resting-state network segregation decreased linearly with increasing age, extending prior reports of de-differentiation across the lifespan. Critically, a more positive valence bias was related to lower segregation of the default mode network (DMN), due to stronger functional connectivity of the DMN with CO and, to a lesser extent, the ventral attention network (VAN) in all participants. In contrast to this overall segregation effect, in participants over 39 years old (who tend to show a positive valence bias), bias was also related to weaker connectivity between the DMN and Reward networks. The present findings indicate that specific interactions between the DMN, a task control network (CO), an emotion processing network (Reward), and, to a weaker extent, an attention network (VAN), support a more positive valence bias, perhaps through regulatory control of self-referential processing and reduced emotional reactivity in aging. The current work offers further insight into the functional brain network alterations that may contribute to affective well-being and dysfunction across the lifespan.more » « less
-
Abstract Many cognitive and sensory processes are characterized by strong relationships between the timing of neuronal spiking and the phase of ongoing local field potential oscillations. The coupling of neuronal spiking in neocortex to the phase of alpha oscillations (8-12 Hz) has been well studied in nonhuman primates but remains largely unexplored in other mammals. How this alpha modulation of spiking differs between brain areas and cell types, as well as its role in sensory processing and decision making, are not well understood. We used Neuropixels 1.0 probes to chronically record neural activity from somatosensory cortex, prefrontal cortex, striatum, and amygdala in mice performing a whisker-based selective detection task. We observed strong spontaneous alpha modulation of single-neuron spiking activity during inter-trial intervals while mice performed the task. The prevalence and strength of alpha phase modulation differed significantly across regions and between cell types. Phase modulated neurons exhibited stronger responses to both go and no-go stimuli, as well as stronger motor- and reward-related changes in firing rate, than their unmodulated counterparts. The increased responsiveness of phase modulated neurons suggests they are innervated by more diverse populations. Alpha modulation of neuronal spiking during baseline activity also correlated with task performance. In particular, many neurons exhibited strong alpha modulation before correct trials, but not before incorrect trials. These data suggest that dysregulation of spiking activity with respect to alpha oscillations may characterize lapses in attention.more » « less
-
Abstract Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala neurons responded earlier than dmPFC neurons, reflecting the bottom-up process for ambiguity processing. We further found parietal-frontal coherence and delta-alpha cross-frequency coupling involved in encoding emotion ambiguity. We replicated the EEG coherence result using independent experiments and further showed modulation of the coherence. EEG source connectivity revealed that the dmPFC top-down regulated the activities in other brain regions. Lastly, we showed altered behavioral responses in neuropsychiatric patients who may have dysfunctions in amygdala-PFC functional connectivity. Together, using multimodal experimental and analytical approaches, we have delineated a neural network that underlies processing of emotion ambiguity.more » « less
