Convergence and interaction of hippocampal and amygdalar projections within the prefrontal cortex in the rat

Abstract

The orbital and medial prefrontal cortex (OMPFC) receives inputs from the CA1/subicular (CA1/S) region of the ventral hippocampus and the basolateral nucleus of the amygdala (BLA). Despite many studies about these projections, little is known as to how CA1/S and BLA inputs converge and interact within the OMPFC. Extracellular recordings of single-unit activity in the OMPFC were performed in sodium pentobarbitone-anesthetized rats. OMPFC neurons driven by CA1/S or BLA stimulation were more frequently encountered in the ventral portion of the prelimbic (v-PrL) and infralimbic cortex (IL). OMPFC neurons showing excitatory convergence of both inputs from the CA1/S and BLA were also located predominantly in the v-PrL and IL. The excitatory latencies of these neurons from both the CA1/S and BLA revealed almost identical values. Excitatory responses of OMPFC neurons to CA1/S (or BLA) stimulation were markedly augmented by simultaneous BLA (or CA1/S) stimulation, whereas the inhibitory influence of the BLA (or CA1/S) on CA1/S-induced (or BLA-induced) excitation was apparent when BLA (or CA1/S) stimulation was given 20-40 msec before CA1/S (or BLA) stimulation. Similar results were also observed when reciprocal connections between the CA1/S and BLA were severed to exclude the influences of these connections on one another. From these studies, we concluded that excitatory and inhibitory inputs from the hippocampus and amygdala converge and interact in the v-PrL and IL. Furthermore, the results indicate that simultaneous activation of hippocampal and amygdalar neurons may be important for amplification of OMPFC neuronal activity.

Figure 5.

Extent of lesioned sites (A) and effects of the lesions on field potentials of the BLA, CA1/S, and IL evoked by CA1/S (B) or BLA (C) stimulation. A, Lesioned areas characterized by apparent loss of tissue integrity and bleeding were enclosed by thick lines (4 rats), all of which were along the base of the brain and included the ventral edge of the ventral hippocampus, AHiPM, PMCo, APir, and LEnt. The values represent the distance from bregma. B, C, Top, The relationship between stimulus intensity and amplitudes of field potentials. Open and filled circles show amplitudes of the field potentials before and after the lesions, respectively. Bottom, Samples of field potentials evoked by each stimulation at 0.3 mA with a 0.1 msec duration before (left) and after (right) the lesions. Asterisks show the time of stimulation. Regarding the field potentials of the BLA evoked by CA1/S stimulation (B-1), the amplitudes of the second negative-going component are plotted (top).

Figure 6.

Examples of OMPFC neurons that revealed facilitation (A, top) and inhibition (A, bottom) of the firing probability of CA1/S-induced excitatory responses after the conditioning stimulation of the BLA and the time course of the facilitatory (B, top) and inhibitory (B, bottom) effects of BLA (or CA1/S) stimulation on excitatory responses to CA1/S (or BLA) stimulation. A, These recordings were obtained in the lesioned rats in which field potentials of the CA1/S (or BLA) evoked by BLA (or CA1/S) stimulation completely disappeared after the lesions. These neurons were located in the IL (A, top) and v-PrL (A, bottom), respectively. ^*, BLA stimulation; Δ, CA1/S stimulation. The time under PSTHs shows ISIs. The PSTH in the left end at the top represents responses to subthreshold BLA stimulation, which by itself evoked no response. The second PSTH from the left end at the top and PSTH in the left end at the bottom show responses to single CA1/S stimulation. B, In each graph, filled (top, n = 16; bottom, n = 17) and open (top, n = 10; bottom, n = 13) circles represent firing probability of OMPFC neurons to CA1/S and BLA stimulation, respectively. The filled and open circles of the left end and horizontal dotted lines represent firing probability to a single CA1/S and BLA stimulation. ^*p < 0.05; ^**p < 0.01; ^***p < 0.0001; compared with firing probability to single CA1/S or BLA stimulation.

Figure 1.

A-C, Excitatory (A) and inhibitory (B) responses of OMPFC neurons to CA1/S or BLA stimulation, and antidromic responses (C) of OMPFC neuron to BLA stimulation. A, Top, Evoked spikes resulting from CA1/S (A-1, A-2) and BLA (A-3) stimulation. An OMPFC neuron (A-1) located in the d-PrL showed more variable latencies compared with those of a neuron (A-2) in the v-PrL. The excitatory latencies of these neurons were 50 msec (A-1) and 18 msec (A-2), respectively. BLA stimulation excited a v-PrL neuron (A-3) at a latency of 14 msec. Arrowheads indicate stimulus artifacts. In all traces, five sweeps are superimposed. A, Bottom, Peristimulus time histograms (PSTHs) of the evoked responses presented in the top. Each PSTH was compiled by 50 (A-1) and 20 (A-2, A-3) sweeps with a 1 msec bin width. B, Inhibitory responses of v-PrL (B-1) and IL (B-2) neurons to CA1/S and BLA stimulation. Each PSTH was compiled of 39 (B-1) and 55 (B-2) sweeps with a 5 msec bin width. Both neurons revealed a prolonged, complete inhibition lasting 195 msec (B-1) and 310 msec (B-2), respectively. In all PSTHs in A and B, stimuli were delivered at 0 msec. C, A v-PrL neuron showed an antidromic response to BLA stimulation at a latency of 20 msec. In the first trace, five sweeps are superimposed. The lowest trace indicates a collision of an antidromic spike with a spontaneous spike (^*).

Figure 2.

A, B, Distribution of OMPFC neurons responding to CA1/S (A) and BLA (B) stimulation. Neurons driven by CA1/S stimulation (^*) were primarily located in the v-PrL and IL, whereas neurons that revealed an inhibitory response to CA1/S stimulation (○) were located homogeneously in the OMPFC. A similar distribution was observed in neurons responding to BLA stimulation. The values represent the distance from bregma. ^*, Excitation; ○, inhibition; ▪, excitation and inhibition.

Figure 3.

A, B, Relationship between excitatory latencies to CA1/S (A) or BLA (B) stimulation and firing probability (top) or SD of the excitatory latency (bottom). The excitatory latencies to CA1/S or BLA stimulation were highly correlated with the SD of the latencies. •, Cg1, d-PrL, and DP-VO neurons; ○, v-PrL-MO and IL neurons. v-PrL-MO and IL neurons are distributed in the range of small SDs.

Figure 4.

A, B, Distribution of neurons showing excitatory and inhibitory convergences (A) and the correlation of excitatory (B, top) or inhibitory (B, bottom) latencies. Neurons driven by both CA1/S and BLA stimulation were primarily located in the v-PrL and IL. The excitatory but not inhibitory latencies to CA1/S and BLA stimulation revealed a strong positive correlation. A, Asterisk, Neurons driven by both CA1/S and BLA stimulation; ○, neurons that revealed inhibitory responses to both stimulations. B, Top, ○, v-PrL-MO and IL neurons; •, Cg1, d-PrL, and DP neurons.