Hebbian reverberations in emotional memory micro circuits

Abstract

The study of memory in most behavioral paradigms, including emotional memory paradigms, has focused on the feed forward components that underlie Hebb's first postulate, associative synaptic plasticity. Hebb's second postulate argues that activated ensembles of neurons reverberate in order to provide temporal coordination of different neural signals, and thereby facilitate coincidence detection. Recent evidence from our groups has suggested that the lateral amygdala (LA) contains recurrent microcircuits and that these may reverberate. Additionally this reverberant activity is precisely timed with latencies that would facilitate coincidence detection between cortical and sub cortical afferents to the LA. Thus, recent data at the microcircuit level in the amygdala provide some physiological evidence in support of the second Hebbian postulate.

Keywords: amygdala; ensembles; fear; network; recurrent.

Figure 1

Schematic representations of two Hebbian postulates underlying memory formation in the brain. (A) Schematics of Hebbian associative plasticity. Cells that fire together wire together. From left to right: Presynaptic cell (black) does not activate post synaptic cell when firing on own. When two presynaptic cells fire simultaneously post synaptic cell fires action potential. This coincident firing of two presynaptic cells leads to synaptic strengthening. Now when the same presynaptic cell fire on own (red) it now activates the post synaptic cell. (B) Schematic of the second Hebbian postulate: reverberating ensemble of neurons. From left to right: The network may reverberate when a sensory signal (black arrow) enters at one node in an interconnected neurons ensemble (grey small arrows). This signal will remain active in the ensemble by moving from neuron to neuron within the network. The path of transmission will vary depending upon neurons’ history of activity, current synaptic strengths and other sensory signals entering the network. Thus, reverberation may follow different paths at each iteration. This reverberant activity can become coincident with new neural signals (middle, black arrows), thereby facilitating ‘Hebbian postulate one’ plasticity at some synapses in the network (in red).

Figure 2

Auditory information convergence in the lateral amygdala (LA). An auditory signal reaches the auditory thalamus in 7–9 ms. From there, it is sent to the lateral amygdala (LA) either directly (‘low road’), or via a longer route, through the auditory cortices, for higher processing of the auditory signal, therefore providing the LA with more detailed information (‘high road’). Therefore, information processed through the high road (blue) reaches the LA later than the direct thalamic processed information (green). Cells in the LA are interconnected and provide a recurrent structure for possible reverberating activity in the LA, facilitating coincidence detection between afferent information and intra-amygdala processing, thus enabling Hebbian plasticity for storage of emotional memory traces in the LA.

Figure 3

Field potentials (in red) evoked in the lateral amygdala (LA) by stimulation of auditory afferents (internal capsula in vitro, auditory thalamus in vivo) showed multiple negative potentials both in vitro (slice) and in vivo (awake rat). Scale: 0.1 mV, 10 ms. These waves represent a monosynaptic response (N1) followed by polysynaptic activity. We developed a method for fitting and extracting peaks that represent reliable synchronized activity (in black). Five and nine peaks were isolated in the slice and the awake preparation, respectively. Note that not all peaks are present in a given sample (e g. here N5 is missing for the in vitro example, or N7 for the in vivo example). To enable comparison between the two preparations, latencies of each of the isolated peaks were normalized with respect to the latency of the first monosynaptic peak (N1). This transformation showed a high correlation between the two preparations (r2 = 0.994; P < 0.005), suggesting similar intra-network rhythmicity in both preparations, and therefore similar network behavior.

Figure 4

Plasticity of recurrent intra-amygdala network. (A) High-frequency stimulation (HFS) of thalamic afferents produces long-term potentiation (LTP) of the monosynaptic field potential response recorded in the superior part of the LAd, a potentiation that lasted at least 90 min. At the same time, long-term depression (LTD) of the intra-LA network was observed. This was evidenced by a depression of the monosynaptic field potential evoked in the superior part of LAd (LAd-s) in response to the stimulation of the inferior part of the LAd (LAd-i) (B); This was also observed as a general decrease in the amplitude of polysynaptic peaks (filled red dots), representing LTD in the network activity (C).