Cell-specific synaptic plasticity induced by network oscillations

Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave- ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner

Die funktionelle Bedeutung von Projektionszellen des medialen entorhinalen Cortex in der Interaktion zwischen entorhinalem Cortex und Hippocampus

Der entorhinale Cortex (EC) nimmt eine zentrale Stellung im limbischem System ein und ist darüber hinaus eine Verbindungsstelle zwischen Hippocampus und Cortex. Um die Eigenschaften der Projektionszellen im EC genauer zu charakterisieren, führten wir intrazelluläre Ableitungen an den Neuronen der oberflächlichen (Schicht II und III) und der tiefen (Schicht IV-VI) Schichten durch, von denen etwa ein Viertel während der Ableitung mit dem Farbstoff Biozytin gefärbt werden konnten. In Schicht III des medialen EC fanden wir vier unterschiedliche Zelltypen, von denen zwei als Projektionsneurone (Typ 1 und Typ 2) charakterisiert wurden. Die Projektionszellen der Schicht III besitzen eine niedrige Schwelle zur Auslösung synaptisch evozierter Aktionspotentiale. Daneben konnten wir zwei weitere Typen von Zellen (Typ 3 und Typ 4) bestimmen, deren Somata in der Schicht III lagen, die aber nicht in den Hippocampus projizierten, sondern lokal im EC verschaltet waren. In den tiefen Schichten des EC fanden sich zur Area Dentata (AD) projezierende bipolare und multipolare Neurone, die trotz der morphologischen Ähnlichkeit mit GABAergen Interneuronen die typischen elektrophysiologischen und neurochemischen Eigenschaften von Prinzipalzellen des EC besitzen. Diese Neurone können vermutlich Funktionen von sowohl Lokal- als auch Projektionszellen übernehmen und dementsprechend die schnelle Informationsübertragung zwischen den tiefen und oberflächlichen Schichten einerseits und zwischen EC und AD andererseits ausüben. Um der Frage nachzugehen, unter welchen Bedingungen die Schicht II- und III-Projektionszellen aktiviert werden, führten wir repetitive synaptische Reizungen im EC durch. Hochfrequente repetitive synaptische Reizung (> 10 Hz) führt zu einer bevorzugten Aktivierung der Schicht II-Zellen. Hingegen werden die Schicht III-Zellen bei niedrigeren Reizfrequenzen (10 Hz) synaptic activation of the EC was more effective at eliciting action potentials from layer II EC neurons. In contrast, during low frequency

Sharp wave and gamma network oscillations within the subiculum.

<p>(A) Spectrogram (top) with color-coded power spectral density (PSD) exemplifies the transition from spontaneously occurring sharp wave-ripples (SWR) to gamma frequency oscillations within the subiculum. The corresponding LFP recordings are displayed below. The application of kainic acid (KA, onset is marked by black line) abolishes the SWR rhythm and induces, after a brief transitory state, a stable oscillatory gamma rhythm. The recording interruptions of the top spectrograms and the underlying LFP traces are 12 s (middle) and 25 min (right). Red lines mark three examples that are illustrated below with higher temporal resolution (SWR, transition, gamma). (A, bottom, left) The SWR (filtered 2–300 Hz), the corresponding SPW (2–50 Hz) and the ripple components (100–300 Hz) supplemented by the color-coded power spectral density wavelet transform. (A, bottom, right) The boxplot depicts the distribution of the wavelet peak power spectral frequencies of 100 analyzed consecutive ripple events of the upper example trace. (B) Sharp waves of both polarities are exemplified on the left with each SWR trace (2–300 Hz, top), the ripple trace (100–300 Hz, middle) and the corresponding wavelet transform as color-coded power spectral density plot (bottom). The boxplot (right) illustrates the distribution of the mean SWP rates of all slices investigated (n = 42).</p

Gamma frequency network oscillations within the subiculum.

<p>(A) Gamma frequency oscillations were found in all of the examined subicular regions (middle, ventral, and dorsal). Sketches illustrate horizontal (middle, ventral and dorsal) slice preparation. The position of the scissors indicate the cuts made around the perimeters of the subicular region with the resulting subicular minislices marked by an asterisk. (A, right next to the sketch) Two example LFP recordings obtained from intact (grey, I, top trace) and isolated (black, II, bottom trace) middle (top), ventral (middle) and dorsal (bottom) slices are displayed together with the corresponding power spectra (A, middle column, color code according to the example traces). (A, right) The population data of the oscillatory frequency (top histogram) and spectral power (bottom histogram) exhibits no significant difference of the intact compared to the isolated subicular slices in network oscillatory gamma frequency as well as in spectral power (values and numbers in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123636#pone.0123636.t001" target="_blank">Table 1</a>) except for the ventral subicular slices (<i>p</i> = 0.034, significance level indicated by asterisk). (B) Gamma frequency oscillations recorded from the medial (grey, I) and lateral (black, II) subiculum within the sagittal slice preparations. Same type of illustration as in (<i>A</i>), the subicular region is marked by an asterisk. The population histogram for frequency and power (values and numbers in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123636#pone.0123636.t002" target="_blank">Table 2</a>) did not reveal a significant difference.</p