The Amygdala Responds Rapidly to Flashes Linked to Direct Retinal Innervation: A Flash-evoked Potential Study Across Cortical and Subcortical Visual Pathways.

Rapid detection and response to visual threats are critical for survival in animals. The amygdala (AMY) is hypothesized to be involved in this process, but how it interacts with the visual system to do this remains unclear. By recording flash-evoked potentials simultaneously from the superior colliculus (SC), lateral posterior nucleus of the thalamus, AMY, lateral geniculate nucleus (LGN) and visual cortex, which belong to the cortical and subcortical pathways for visual fear processing, we investigated the temporal relationship between these regions in visual processing in rats. A quick flash-evoked potential (FEP) component was identified in the AMY. This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC, which was assumed to be an important area in visual fear. This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection, but was diminished by RU38486, a glucocorticoid receptor blocker. By injecting a monosynaptic retrograde AAV tracer into the AMY, we found that it received a direct projection from the retina. These results confirm the existence of a direct connection from the retina to the AMY, that the latency in the AMY to flashes is equivalent to that in the sensory thalamus, and that the response is modulated by glucocorticoids.

Reversible olfactory dysfunction impaired learning and memory with impaired hippocampal synaptic plasticity and increased corticosterone release in mice.

Olfactory dysfunction is related with various neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease and Parkinson's disease, which show impaired cognitive functions. However, the effects of olfactory dysfunction on hippocampal dependent learning and memory remain elusive. In this study, mice were treated with intranasal zinc sulfate (ZnSO4) infusion which resulted in a complete but reversible loss of olfactory function. Olfaction was totally destroyed even 1 week after zinc sulfate treatment, but partially recovered 4 weeks later. We found learning and memory in Y-maze and fear conditioning were not affected by ZnSO4 1 week after the treatment, but learning and memory were severely destroyed 4 weeks later. Electrophysiology results showed impaired hippocampal long-term potentiation and long-term depression 4 weeks after the olfaction dysfunction, while only long-term depression was impaired 1 week after the treatment. Western blot showed that the expression and phosphorylation of GluA1 in zinc group did not show any increase after fear conditioning as the control mice. Serum corticosterone release was increased in olfactory deficit mice at baseline and after acute stress when tested 3, 10 and 20 days after the olfactory dysfunction. All these results indicated that reversible olfactory dysfunction elicited impaired hippocampal function in mice. The higher corticosterone release after olfactory deficiency might serve as an underling mechanism.

Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring.

Advanced maternal or paternal age is associated with increased risks of cognitive and emotional disorders. Chronic stress is also a common experience in human life that causes psychiatric diseases. However, the synergistic effects of these two factors on offspring are rarely studied. In the present study, the offspring of both young (3-4 months) and old (12-14 months) rat parents were given CUMS for 21 days at the age of 4 weeks. The effects of advanced parental age and chronic unpredictable mild stress (CUMS) on emotional and cognitive behaviors and the related cellular mechanisms were investigated by using behavioral and electrophysiological techniques. We found that CUMS decreased sucrose consumption, increased anxiety, and impaired learning and memory in offspring from both old and young breeders. However, advanced parental age impaired fear memory and spatial memory mainly in female offspring. The serum corticosterone of female offspring was lower than males, but advanced parental age significantly elevated serum corticosterone in female offspring in response to electrical foot shocks. In addition, hippocampal LTD was severely impaired in female offspring from older parents. Our results indicated that female offspring from older breeders might be more sensitive to stress, and the hippocampal function was more vulnerable. These results might provide experimental basis for the prevention and treatment of advanced parental age related psychiatric disorders in future.

Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus.

D1-like dopamine receptor dysfunction in the lateral habenula nucleus increased anxiety-like behavior in rat.

Lateral habenula (LHb) is important for emotional processing. It is a link node between forebrain and midbrain. LHb is reciprocally connected with ventral tegmental area, acting as a regulatory center for the dopaminergic system. However, the role of dopamine receptors in the LHb in emotional processing is less clear. In the present study, the expression of dopamine D1 and D2 receptors in LHb was testified by western blot. In addition, D1- or D2-like receptor agonist or antagonist was bilaterally administered into the LHb, anxiety-like and depressive-like behaviors were tested 15min later in rats. In addition, the effects of LHb dopamine receptor activation and inactivation on aversive learning and memory were assessed. Our results showed that: (1) activation and inhibition of D1R but not D2R in LHb increased anxiety-like behavior but decreased depressive-like behavior in rats. (2) D1R activation and inactivation in LHb impaired aversive memory acquisition but not consolidation in rats, D1R agonist also impaired aversive memory retrieval in rats. These results might provide new clues about how LHb was involved in emotional processing.