Biology subjects

Goode, T. D.

Publications and source records attributed to Goode, T. D..

5 recordsLinked to original sources

bioRxiv2025

Neotenic expansion of adult-born dentate granule cells reconfigures GABAergic inhibition to enhance social memory consolidation

Adult-born dentate granule cells (abDGCs) contribute to hippocampal dentate gyrus (DG)-CA3/CA2 circuit functions in memory encoding, retrieval and consolidation. Heightened synaptic and structural plasticity of immature abDGCs is thought to govern their distinct contributions to circuit and network mechanisms of hippocampal-dependent memory operations. Protracted maturation or neoteny of abDGCs in higher mammals is hypothesized to offset decline in adult hippocampal neurogenesis by expanding the capacity for circuit and network plasticity underlying different memory operations. Here, we provide evidence for this hypothesis by genetically modelling the effective impact of neoteny of abDGCs on circuitry, network properties and social cognition in mice. We show that selective synchronous expansion of a single cohort of 4 weeks old immature, but not 8 weeks old mature abDGCs, increases functional recruitment of fast spiking parvalbumin expressing inhibitory interneurons (PV INs) in CA3/CA2, number of PV IN-CA3/CA2 synapses, and GABAergic inhibition of CA3/CA2. This transient increase in feed-forward inhibition in DG-CA2 decreased social memory interference and enhanced social memory consolidation. In vivo local field potential recordings revealed that the expansion of a single cohort of 4-week-old abDGCs increased baseline power, amplitude, and duration, as well as sensitivity to social investigation-dependent rate changes of sharp-wave ripples (SWRs) in CA1 and CA2, a neural substrate for memory consolidation. Inhibitory neuron-targeted chemogenetic manipulations implicate CA3/CA2 INs, including PV INs, as necessary and sufficient for social memory consolidation following neotenic expansion of the abDGC population and in wild-type mice, respectively. These studies suggest that neoteny of abDGCs may represent an evolutionary adaptation to support cognition by reconfiguring PV IN-CA3/CA2 circuitry and emergent network properties underlying memory consolidation.

neuroscience↗

bioRxiv2024

A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding

Adaptive regulation of feeding depends on linkage of internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation of a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation of underlying cell-types and circuitry is lacking. Here, we identify an evolutionary conserved and discrete Prodynorphin (Pdyn)-expressing subpopulation of Somatostatin (Sst)-expressing inhibitory neurons in the dorsolateral septum (DLS) that receives primarily dorsal, but not ventral, hippocampal inputs. DLS(Pdyn) neurons inhibit LHA GABAergic neurons and confer context- and internal state-dependent calibration of feeding. Viral deletion of Pdyn in the DLS mimicked effects seen with optogenetic silencing of DLS Pdyn INs, suggesting a potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling in contextual regulation of food-seeking. Together, our findings illustrate how the dorsal hippocampus has evolved to recruit an ancient LHA feeding circuit module through Pdyn DLS inhibitory neurons to link contextual information with regulation of food consumption. HIGHLIGHTSO_LIDLS(Pdyn) neurons receive dense input from the dorsal but not ventral hippocampus C_LIO_LIDLS(Pdyn) neurons inhibit GABAergic neurons in the LHA C_LIO_LISilencing dorsal hippocampus-DLS(Pdyn)-LHA circuit nodes abolishes context-conditioned feeding C_LIO_LIPdyn in the DLS is necessary for context-conditioned feeding C_LI

neuroscience↗

bioRxiv2024

An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience

Breakdown of lipid homeostasis is thought to contribute to pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimers Disease (AD). Cognitive reserve theory posits a role for compensatory mechanisms in the aging brain in preserving neuronal circuit functions, staving off cognitive decline, and mitigating risk for AD. However, the identities of such mechanisms have remained elusive. A screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors identified a secreted phospholipase, Pla2g2f, whose expression increases in DGCs during aging. Pla2g2f deletion in DGCs exacerbates aging-associated pathophysiological changes including synapse loss, inflammatory microglia, reactive astrogliosis, impaired neurogenesis, lipid dysregulation and hippocampal-dependent memory loss. Conversely, boosting Pla2g2f in DGCs during aging is sufficient to preserve synapses, reduce inflammatory microglia and reactive gliosis, prevent hippocampal-dependent memory impairment and modify trajectory of cognitive decline. Ex vivo, neuronal-PLA2G2F mediates intercellular signaling to decrease lipid droplet burden in microglia. Boosting Pla2g2f expression in DGCs of an aging-sensitive AD model reduces amyloid load and improves memory. Our findings implicate PLA2G2F as a compensatory neuroprotective factor that maintains lipid homeostasis to counteract aging-associated cognitive decline.

neuroscience↗

bioRxiv2019

Threat imminence dictates the role of the bed nucleus of the stria terminalis in contextual fear

Previous work indicates that the bed nucleus of the stria terminalis (BNST) is involved in defensive freezing to unpredictable Pavlovian conditioned stimuli (Goode et al., 2019). Here we show that the BNST mediates freezing to contexts paired with remote (unpredictable), but not imminent (predictable), footshock. Rats underwent a fear conditioning procedure in which a single footshock unconditioned stimulus (US) was delivered either 1 (imminent) or 9 minutes (remote) after placement in the context; each rat received a total of four conditioning trials over two days. Contexts associated with either imminent or remote USs produced distinct patterns of freezing and shock-induced activity but freezing in each case was context-dependent. Reversible inactivation of the BNST reduced the expression of contextual freezing in the context paired with remote, but not imminent, footshock. Implications of these data are discussed in light of recent conceptualizations of BNST function, as well as for anxiety behaviors.

neuroscience↗

bioRxiv2018

Bed nucleus of the stria terminalis mediates fear to ambiguous threat signals

The bed nucleus of the stria terminalis (BNST) has been implicated in fear and anxiety, but the specific factors that engage the BNST in defensive behavior are unclear. Here we explore the possibility that ambiguous threats recruit the BNST during Pavlovian fear conditioning in rats. We arranged a conditioned stimulus (CS) to either precede or follow an aversive unconditioned stimulus (US), a procedure that established reliable (forward) or ambiguous (backward) signals for US onset. After conditioning, reversible inactivation of the BNST selectively reduced freezing to the backward CS; BNST inactivation did not affect freezing to the forward CS even when that CS predicted a variable magnitude US. Backward CSs increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic cortex, but not the hippocampus or amygdala. These data reveal that BNST circuits process ambiguous threat signals central to the etiology and expression of anxiety.

neuroscience↗