Past events

Episodic memory – the ability to encode, maintain and retrieve information – is critical for everyday functioning at all ages, yet little is known about the development of episodic memory systems and their brain substrates. In this talk, I will present data from a series of studies with which we begin to identify how brain development underlies changes in episodic memory throughout childhood and adolescence. Using structural MRI data, I will present evidence demonstrating how brain development sets limits on cognitive developmnet. I will show that individual differences in fine structural measures of the hippocampus, a region known to be critical for episodic memory, and the prefrontal cortex (PFC), a region that shows protracted structural development, partially explain age-related improvement in episodic memory. Using functional neuroimaging methods including functional MRI (fMRI) and electrocorticography (ECoG), I will present our ongoing attempts to characterize the neural correlates of episodic memory development. Evidence from fMRI studies suggest that age differences in episodic memory functioning may primarily relate to age differneces in PFC activation and connectivity patterns. Intracranial evidence further underscores the role of the PFC in memory and reveals that spatiotemporal propagation of frontal activity supports memory formation in children. I will highlight the challenges in investigaitons of brain-behavior relations in pediatric populations and discuss how advances in methodologies provide unique opportunities for moving towards a mechanistic understanding of developmental changes.

Over the course of a natural day-night cycle, mean luminance levels can span ten log units or more. Mammalian retinas effectively encode visual information over this vast range, in part by utilizing exquisitely sensitive rod photoreceptors in dim conditions and multiple color-variant cone photoreceptors in bright conditions. These visual signals, regardless of origin, must pass through a common set of retinal ganglion cells, thereby creating opportunities for signal interactions. Human perceptual experiments conducted under intermediate lighting conditions reveal constructive and destructive interactions between flickering rod and cone stimuli that are thought to originate in the retina. In support of this hypothesis, we find rod-cone flicker interference in On and Off retinal ganglion cells that project! to magnocellular visual pathways in primates. The dependence of this interference on the frequency and phase of the temporal modulation is similar to that observed in perceptual measurements. Recordings from within the retinal circuitry indicate that rod-cone signal interference reflects a linear combination of kinetically-distinct rod and cone signals upstream of the ganglion cell synaptic inputs. Ultimately, using our empirically-derived data as a foundation, we construct a mathematical model that recapitulates known rod-cone interactions and predicts retinal output in response to a broad range of time-varying rod and cone stimuli.

Background: The aim of anaesthesia is to eliminate awareness and prevent memory of the various aversive stimuli of medical procedures. Yet in a portion of cases, patients can recall events that occurred during surgery resulting in risks of adverse psychological outcomes. Fear conditioning offers a robust behavioral model to study this phenomenon, while the abundant evidence implicating the amygdala-medial prefrontal cortex (mPFC) circuit in acquisition, consolidation and retrieval of these memories offers a natural hypothesis for the neural mechanisms. Objective: We aimed to study the effect of anaesthesia on stimulus valence, acquisition and memory and to identify the correlates in the mPFC-amygdala circuit using a primate model and clinically relevant doses of anesthesia. Materials and methods: Two non-human primates acquired aversive memories by tone-odor classical conditioning under anesthesia with different doses of ketamine, a non-competitive antagonist of NMDA and midazolam, a GABA agonist. Both agents are in wide clinical use. We simultaneously recorded single neurons in the BLA and mPFC. Analyses focused on behavioral and neural evidence suggesting maintained valence, acquisition and retention of memory. Results: Seventy-six full sessions from two non-human primates entered analysis. We recorded 172 amygdala and 189 dACC neurons respectively. We found evidence of successful aversive conditioning under both anesthetics and in all doses. Under anesthesia, we found behavioral evidence of retention in 46% of sessions matched by a complementary response of 16.2% and 18.7% of amygdala and mPFC neurons respectively. An increased and escalating amygdala and mPFC response during acquisition predicted later retention and correlated the behavioral result. The behavioral and neural representation of aversive valence was sufficient to drive learning and affected conditioning outcome. Conclusion: Our results suggest that under anesthesia, the perception of stimuli and implicit aversive memory formation may be maintained. We show patterns in the amygdala-mPFC circuit that precede and predict this phenomenon and that may serve future monitoring strategies of anesthetized patients. The use of a primate model and therapeutic doses of common anesthetics affecting both GABA and NMDA transmission improves the possible translation of our findings.

Over the course of a natural day-night cycle, mean luminance levels can span ten log units or more. Mammalian retinas effectively encode visual information over this vast range, in part by utilizing exquisitely sensitive rod photoreceptors in dim conditions and multiple color-variant cone photoreceptors in bright conditions. These visual signals, regardless of origin, must pass through a common set of retinal ganglion cells, thereby creating opportunities for signal interactions. Human perceptual experiments conducted under intermediate lighting conditions reveal constructive and destructive interactions between flickering rod and cone stimuli that are thought to originate in the retina. In support of this hypothesis, we find rod-cone flicker interference in On and Off retinal ganglion cells that project! to magnocellular visual pathways in primates. The dependence of this interference on the frequency and phase of the temporal modulation is similar to that observed in perceptual measurements. Recordings from within the retinal circuitry indicate that rod-cone signal interference reflects a linear combination of kinetically-distinct rod and cone signals upstream of the ganglion cell synaptic inputs. Ultimately, using our empirically-derived data as a foundation, we construct a mathematical model that recapitulates known rod-cone interactions and predicts retinal output in response to a broad range of time-varying rod and cone stimuli.

Background: The aim of anaesthesia is to eliminate awareness and prevent memory of the various aversive stimuli of medical procedures. Yet in a portion of cases, patients can recall events that occurred during surgery resulting in risks of adverse psychological outcomes. Fear conditioning offers a robust behavioral model to study this phenomenon, while the abundant evidence implicating the amygdala-medial prefrontal cortex (mPFC) circuit in acquisition, consolidation and retrieval of these memories offers a natural hypothesis for the neural mechanisms. Objective: We aimed to study the effect of anaesthesia on stimulus valence, acquisition and memory and to identify the correlates in the mPFC-amygdala circuit using a primate model and clinically relevant doses of anesthesia. Materials and methods: Two non-human primates acquired aversive memories by tone-odor classical conditioning under anesthesia with different doses of ketamine, a non-competitive antagonist of NMDA and midazolam, a GABA agonist. Both agents are in wide clinical use. We simultaneously recorded single neurons in the BLA and mPFC. Analyses focused on behavioral and neural evidence suggesting maintained valence, acquisition and retention of memory. Results: Seventy-six full sessions from two non-human primates entered analysis. We recorded 172 amygdala and 189 dACC neurons respectively. We found evidence of successful aversive conditioning under both anesthetics and in all doses. Under anesthesia, we found behavioral evidence of retention in 46% of sessions matched by a complementary response of 16.2% and 18.7% of amygdala and mPFC neurons respectively. An increased and escalating amygdala and mPFC response during acquisition predicted later retention and correlated the behavioral result. The behavioral and neural representation of aversive valence was sufficient to drive learning and affected conditioning outcome. Conclusion: Our results suggest that under anesthesia, the perception of stimuli and implicit aversive memory formation may be maintained. We show patterns in the amygdala-mPFC circuit that precede and predict this phenomenon and that may serve future monitoring strategies of anesthetized patients. The use of a primate model and therapeutic doses of common anesthetics affecting both GABA and NMDA transmission improves the possible translation of our findings.

The normal function of alpha-synuclein, a protein involved in Parkinson's Disease and other synucleinopathies, remains elusive. Though recent studies suggest that alpha-synuclein is a physiological attenuator of synaptic vesicle recycling, mechanisms remain unclear. Our data show that synapsin – a cytosolic protein with established roles in synaptic vesicle mobilization and clustering – is required for alpha-synuclein function. Furthermore, we show that the two proteins interact in a reversible manner in the synapse and that in the absence of synapsins, the localization of alpha-synuclein to synapses is deficient. Our data suggest a model where alpha-synuclein and synapsin cooperate in clustering SVs and attenuating recycling.