Modulation by pregnenolone sulfate of filtering properties in the hippocampal trisynaptic circuit

Abstract

Short-term synaptic plasticity alters synaptic efficacy on a timescale that is relevant to encoding information in spike trains. The dynamics of this plasticity, combined with that of the feedback and feedforward contributions of local interneurons, impose frequency-dependent properties on neuronal networks with implications for nervous system function. The trisynaptic network of the hippocampus is especially well suited to selectively filter components of frequency-dependent signals that are transmitted from the entorhinal cortex. We measured presynaptic [Ca2+]i in perforant path, mossy fiber, or Schaffer collateral terminals while simultaneously measuring field potentials of principal cells of the dentate, CA3, or CA1 synaptic fields over a range of stimulus frequencies of 2 to 77 Hz. In all three synaptic fields, the average [Ca2+]i during a 500 ms stimulus train rose monotonically with stimulus frequency. The average population spike amplitude during this stimulus train, however, exhibited a non-linear relationship to frequency that was distinct for each of the three synaptic fields. The dentate synaptic field exhibited the characteristics of a low pass filter, while both CA synaptic fields had bandpass filter characteristics with a gain that was greater than 1 in the passband frequencies. Importantly, alteration of the dynamic properties of this network could significantly impact information processing performed by the hippocampus. Pregnenolone sulfate (PregS), has frequency-dependent effects on paired- and multi-pulse plasticity in the dentate and CA1 synaptic fields of the hippocampal formation. We investigated the PregS-dependent modulation of the dynamic properties of transmission by the principal cells of the three hippocampal synaptic fields. Importantly, PregS is capable of altering the pattern separation capabilities that may underlie hippocampal information processing.

Temporal pattern separation in hippocampal neurons through multiplexed neural codes

“…Figuring out the computations of the DG is equivalent to reverse-engineering the transfer function defining the DG filter. Some have suggested that the DG is a low-pass [22, 76] or a ~10 Hz band-pass filter [21]. Our results confirm that the output frequency of GCs is constrained in a narrow band ( Fig 5B ) and go one step further by providing the first demonstration that the filtering properties of the DG allow it to perform different computations including pattern separation in response to complex naturalistic inputs ( Fig 6 ).…”

Novel functions of GABA signaling in adult neurogenesis

“…In this neuronal network, the trisynaptic circuit of the hippocampal formation, the flow of impulses comes from the entorhinal cortex (EC) and propagates through the DG, CA3 and CA1 regions (Kempermann, 2011; Scullin and Partridge, 2012; Wojtowicz, 2012). This propagation pattern leads to the formation of a loop, with the impulses being transmitted back to the EC.…”

Induction frequency affects cortico-striatal synaptic plasticity with implications for frequency filtering

“…We have previously demonstrated low-pass filter characteristics of layer V glutamatergic inputs to MSNs in the striatum (Jelinek and Partridge, 2012) and provided evidence that GABAergic feedback mechanisms underlie these characteristics. We have also previously shown differential filtering characteristics within the CA3, CA1, and dentate gyrus of the hippocampus (Scullin and Partridge, 2012), indicating that filter properties are a local property of specific brain regions. If this low-pass filtering and synaptic plasticity are a characteristic feature of the cortico-striatal circuitry, it is an interesting and important question to examine how these phenomena may interact.…”