Biology subjects

Briguglio, J.

Publications and source records attributed to Briguglio, J..

3 recordsLinked to original sources

bioRxiv2023

Mechanisms of memory storage and retrieval in hippocampal area CA3

Hippocampal area CA3 is thought to play a central role in memory formation and retrieval. Although various network mechanisms have been hypothesized to mediate these computations, direct evidence is lacking. Using intracellular membrane potential recordings from CA3 neurons and optogenetic manipulations in behaving mice we found that place field activity is produced by a symmetric form of Behavioral Timescale Synaptic Plasticity (BTSP) at recurrent synaptic connections among CA3 principal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not DG was required to update place cell activity based on the animals movement. These data were captured by a computational model that used BTSP and an external updating input to produce attractor dynamics under online learning conditions. Additional theoretical results demonstrate the enhanced memory storage capacity of such networks, particularly in the face of correlated input patterns. The evidence sheds light on the cellular and circuit mechanisms of learning and memory formation in the hippocampus. One Sentence SummaryEvidence from behaving mice points to cellular and circuit mechanisms that underlie observed attractor dynamics in area CA3.

neuroscience↗

bioRxiv2019

The statistical structure of the hippocampal code for space as a function of time, context, and value

Hippocampal activity represents many behaviorally important variables, including context, an animals location within a given environmental context, time, and reward. Here we used longitudinal calcium imaging in mice, multiple large virtual environments, and differing reward contingencies to derive a unified probabilistic model of hippocampal CA1 representations centered on a single feature - the field propensity. Each cells propensity governs how many place fields it has per unit space, predicts its reward-related activity, and is preserved across distinct environments and over months. The propensity is broadly distributed--with many low, and some very high, propensity cells --and thus strongly shapes hippocampal representations. The result is a range of spatial codes, from sparse to dense. Propensity varied ~10-fold between adjacent cells in a salt-and-pepper fashion, indicating substantial functional differences within a presumed cell type. The stability of each cells propensity across conditions suggests this fundamental property has anatomical, transcriptional, and/or developmental origins.

neuroscience↗

bioRxiv2017

Cortical neural activity predicts sensory acuity under optogenetic manipulation.

Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory-inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting differences in circuitry or expression of optogenetic factors. Changes in neural population responses consistently predicted behavioral changes for individuals separately, including improvement and impairment in acuity. This correlation between cortical and behavioral change demonstrates that, despite complex and varied effects these manipulations can have on neuronal dynamics, the resulting changes in cortical activity account for accompanying changes in behavioral acuity.\n\nAuthor summaryExcitatory and inhibitory interactions determine stimulus specificity and tuning in sensory cortex, thereby controlling perceptual discrimination acuity. Modeling of such excitatory-inhibitory circuits has predicted that suppressing the activity of inhibitory neurons can lead to increases or, paradoxically, decreases in excitatory activity, depending on the architecture and modulation parameters of the inhibitory component of the network. Here, we capitalized on differences between subjects to test whether suppressing/activating inhibition and excitation across a range of parameters in sensory cortex can in fact exhibit such paradoxical effects for both stimulus sensitivity and behavioral discriminability. Indeed, we found that the same optogenetic manipulation in the auditory cortices of different mice could improve or impair frequency discrimination acuity, in a fashion that was predictable from the effects on cortical responses to tones. The same manipulations sometimes produced opposite changes in the behavior of different individuals, supporting theoretical predictions for inhibition-stabilized networks.

neuroscience↗